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[Display omitted] • New thiosemicarbazide and 1,2,4-triazole derivatives, not described in the literature, were synthesized. • The anthelmintic activity was tested in vitro and in vivo on four pathogenic nematode species. • The in vivo studies showed no systemic toxicity of the tested compound (II-1). • The degree of inhibition of selected CYP450 enzymes depending on the concentration of the tested compound II-1 was assessed. • The in silico studies indicated tubulin and the SDH enzyme as potential molecular targets of the tested compound (II-1) Intestinal parasitic infections are neglected diseases and, due to the increasing resistance of parasites to available drugs, they pose an increasing therapeutic challenge. Therefore, there is a great need for finding new compounds with antiparasitic activity. Objectives: In this work, new thiosemicarbazide and 1,2,4-triazole derivatives were synthesized and tested for their anthelmintic activity. The synthesis was carried out by classical methods of organic chemistry. Anthelmintic activity tests were carried out in vitro (Rhabditis sp., Haemonchus contortus , Strongylidae sp.) in vivo (Heligmosomoides polygyrus/bakeri), and in silico analysis was performed. Quinoline-6-carboxylic acid derivative compounds were designed and synthesized. The highest activity in the screening tests in the Rhabditis model was demonstrated by compound II-1 with a methoxyphenyl substituent LC 50 = 0.3 mg/mL. In the next stage of the research, compound II-1 was analyzed in the H. contortus model. The results showed that compound II-1 was active and had ovicidal (percentage of dead eggs > 45 %) and larvicidal (percentage of dead larvae > 75 %) properties. Studies in the Strongylidae sp. model confirmed the ovicidal activity of compound II-1 (percentage of dead eggs ≥ 55 %). In vivo studies conducted in the H. polygyrus / bakeri nematode model showed that the number of nematodes decreased by an average of 30 % under the influence of compound II-1. In silico studies have shown two possible modes of action of compound II-1, i.e. inhibition of tubulin polymerization and SDH. The test compound did not show any systemic toxic effects. Its influence on drug metabolism related to the activity of cytochrome CYP450 enzymes was also investigated. The results obtained in the in vitro, in vivo , and in silico studies indicate that the test compound can be described as a HIT, which in the future may be used in the treatment of parasitic diseases in humans and animals. [ABSTRACT FROM AUTHOR]

Today's research is focused on developing new safe drugs of clinical importance. Nitrogen-containing heterocycles are abundant in the common of therapeutic scaffolds. Triazoles are heterocyclic compounds containing a five-membered ring of two carbon atoms and three nitrogen molecules. These structures have sparked enthusiasm for advancing new analogues with miscellaneous biological activities. The need for innovative antifungal drugs is an urgent issue in the current situation where the number of refractory suppressed patients is increasing. This review summarizes research leading to the innovation and progress of latest antifungal agents from a variety of resource during this time. This review primarily focuses on the in vitro and in vivo antifungal activity, design, and SAR of new antifungal agents. • Triazole-based derivatives exhibited potential antifungal activities against tested fungal pathogens. • Detailed explanation of structure-activity relationships (SAR). • EDGs and EWGs play a key role in increasing antifungal activities. • Rational design and development of triazole-based hybrids against fungal pathogens. [ABSTRACT FROM AUTHOR]

• Synthesis, characterization, and computational analysis of novel paramethoxythymol-1,2,3-triazole derivatives. • HRMS and NMR spectroscopy (1H and 13C) were meticulously employed to ensure precise identification of the synthesized compounds. • Density functional theory (DFT) calculations were performed. • Molecular dynamics investigations indicated that the complex between Bcl2 and compound 5b is more stable. This study investigates the synthesis, characterization, and computational analysis of novel paramethoxythymol-1,2,3-triazole derivatives derived from naturally occurring thymol. HRMS and NMR spectroscopy (1H and 13C) were meticulously employed to ensure precise identification of the synthesized compounds. Density functional theory (DFT) calculations were performed to elucidate the stability of the derivatives. In silico docking simulations, molecular dynamics, and ADMET analysis provided insights into the potential interactions between the synthesized molecules and the active sites of Epidermal Growth Factor Receptor (EGFR) and B-cell lymphoma 2 (Bcl2). Docking analysis revealed favorable binding affinities of the 1,2,3-triazole derivatives towards EGFR, with compound 5b exhibiting the most potent interaction, characterized by a docking score of -28.8 kJ/mol. Conversely, compound 6b demonstrated a docking score of -29.2 kJ/mol with Bcl2. Molecular dynamics investigations indicated that the complex between Bcl2 and compound 5b is more stable, suggesting it as a potential candidate for inhibiting Bcl2 protein. These findings suggest that paramethoxythymol-1,2,3-triazole derivatives hold promise as lead candidates for the development of novel targeted anticancer agents. [Display omitted] [ABSTRACT FROM AUTHOR]

• Synthesis of novel phenoxy methyl 1,2,3-triazole derivatives with amide links via click chemistry. • Investigate ADME properties of novel phenoxy methyl triazole derivatives. • Examine antimalarial activity of phenoxy methyl triazole derivatives. • Assess antimicrobial effects of phenoxy methyl triazole derivatives. • Conduct molecular docking studies on phenoxy methyl triazole derivatives. Herein, a new series of phenoxy methyl linked 1,4-disubstituted 1,2,3-triazole derivatives (SR1–SR16) was synthesized by click reaction and copper-catalyzed Huisgen [3 + 2] cycloaddition in the presence of copper sulphate and sodium ascorbate. All the newly synthesized compounds were characterized via Mass, 1H NMR, 13C NMR, FT-IR spectroscopy, and elemental analysis and evaluated for their antimalarial and antimicrobial activities. Among the synthesized compounds, SR12 containing naphthyl substituent is found to be the most active compound with IC 50 of 18.60 μM in antimalarial activities and SR7 and SR9 were found to exhibit good antimicrobial activity at 600.83 μM and 614.12 μM concentration respectively. The antimalarial activity of the synthesized compounds was further supplemented by molecular docking studies against the PfDHFR (PDB ID- 3QGT) receptor, revealing that the remarkable binding affinity values and key interactions as compared to the standard reference Chloroquine. The drug-likeness properties of these compounds were supported by predicted pharmacokinetics. [ABSTRACT FROM AUTHOR]

[Display omitted] • Synthesis of quinoline-fused 1,2,3-triazole hybrids (5a – 5o). • Compounds 5a , 5c , 5f - 5g and 5j had higher activity than the 5-FU against three breast cancer cells. • Compound 5a showed effective inhibition against tyrosine kinase EGFR and HER2. • In silico studies were carried out for in vitro active compounds. Some new quinoline linked fused 1,2,3-triazole hybrids (5a-5o) were synthesized via Cu(I) catalyzed azide-alkyne cycloaddition followed by intramolecular C H arylation in one pot. Further, these derivatives were screened for their anti-breast cancer activity against MCF-7, MDA-MB-468 and MDA-MB-231 cell lines and results were compared with the 5-fluorouracil (5-FU). Out of all, compounds 5a , 5c , 5f , 5g and 5j displayed higher activity than the 5-FU against three cancer cell lines. Compound 5a was more effective in inhibiting both tyrosine kinase EGFR and HER2 enzymes than the Erlotinib and Lapatinib. Furthermore, compound 5j demonstrated greater potency than the Erlotinib against EGFR. Molecular docking studies revealed the important binding features of most potent compounds 5a , 5c , 5f , 5g and 5j with EGFR (PDB ID-4HJO) and HER2 (PDB ID-3RCD) and results were found to be supportive with corresponding IC 50 data. Finally, in silico pharmacokinetic studies revealed that compounds 5a , 5c , 5f , 5g and 5j followed Ghose, Egan, Muegge, Lipinski and Veber rules without any deviation. [ABSTRACT FROM AUTHOR]

Triazole-based Mn(II), Fe(II), Ni(II), Cu(II) and Zn(II) complexes as potential anticancer agents – physicochemical properties, in silico predictions and in vitro activity. [Display omitted] A series of solid-state coordination compounds of Mn(II), Fe(II), Ni(II), Cu(II) and Zn(II) with 5-((1-methyl-pyrrol-2-yl)methyl)-4-(2-chlorophenyl)-1,2,4-triazoline-3-thione as a ligand were synthesized and studied in terms of their chemical composition (elemental analysis, ICP), spectroscopic properties (FTIR) and magnetic measurements. Single crystal X-ray diffraction analysis (SC-XRD), HRMS and NMR studies were carried out to confirm the structure of the organic ligand. Its biological potential was evaluated in silico , using molecular docking studies and ADME analysis. The anticancer activity of all five metal complexes and the organic ligand were tested in vitro against A549 and HT-29 cancer cells. We found that the metal complexes in general exhibited better anticancer activity in comparison with the free ligand, with the Cu(II) complex exhibiting the highest activity against both tested cell lines. [ABSTRACT FROM AUTHOR]

• The N -phenethyl-2-(1 H -1,2,3-triazol-1-yl)acetamide derivatives were synthesized via click chemistry. • The new compounds were confirmed by SCXRD, MS, FTIR and NMR. • Molecular geometries were optimized using DFT method and HOMO–LUMO were calculated. • Molecular docking studies were performed on SARS-CoV-2 proteases 3CLpro and PLpro and Helicase. • Compounds 9, 26 and 12 exhibited excellent binding energy. Novel N -phenethyl-2-(1 H -1,2,3-triazol-1-yl)acetamide derivatives were synthesized via Copper(I)-catalyzed 1,3-dipolar azide-alkyne cycloaddition, commonly known as CuAAC. These triazoles were then characterized using Nuclear Magnetic Resonance (NMR), Fourier Transform Infrared Spectroscopy (FTIR), and Mass Spectrometry (MS). The crystal structures of ten compounds were elucidated through single-crystal X-ray diffraction (SCXRD). Computational calculations, based on Density Functional Theory (DFT), were employed to optimize the molecular structures. The energy levels of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) were also determined. Additionally, molecular docking studies revealed the binding interactions of the most potent triazole with the active sites of key molecular targets. The findings indicated that the newly synthesized triazoles exhibit promising inhibitory activity against SARS-CoV-2 proteases 3-chymotrypsin-like protease (3CLpro), papain-like protease (PLpro), and helicase, outperforming the co-crystallized ligand. [ABSTRACT FROM AUTHOR]

• A series of 1,2,3-triazole derivatives tethered to p-methoxythymol, a natural product was synthesized and further elucidated by detailed analysis of their HRMS, ¹H- and ¹³C NMR spectra. • Molecular docking results were further validated and refined through molecular dynamic (MD) simula. • Network pharmacology screening identifies potential targets for cancer treatment. Cancer prevention has become a major focus of public health in the 21st century. Despite advancements in treatment, tackling cancer remains a significant challenge due to the different types of cancer. Breast cancer stands out as the leading cause of cancer-related deaths, highlighting its significant impact on female health worldwide. Monoterpenes, exemplified by thymol, exhibit notable potential in cancer treatment, owing to their pharmacological properties and mechanisms of action. Concurrently, 1,2,3-triazoles have garnered attention as promising entities for the development of anticancer agents, showcasing their efficacy and relevance in oncology research. This study describes the synthesis and characterization of a novel library of 1,2,3-triazole derivatives tethered to p -methoxythymol, a natural product. High-resolution mass spectrometry (HRMS) definitively confirmed the structures of the synthesized compounds, which were further elucidated by detailed analysis of their ¹H- and ¹³C NMR spectra. To predict the suitable target, network pharmacology was applied to the synthesized thymol derivatives, resulting in the identification of phosphatidylinositol-3-kinase (PIK3CA) as a key target. Furthermore, these thymol derivatives were screened for ADMET and molecular docking against the phosphatidylinositol-3-kinase (PIK3CA) target. Molecular dynamics simulations were conducted for the top two compounds over a duration of 100 ns to assess their stability. The RMSD (Root-Mean-Square Devia-tion) and RMSF (root-mean-square fluctuation) values for amino acid residues indicated structural integrity and stable protein-ligand interaction. Additionally, all designed compounds displayed favorable physicochemical properties and ADMET profiles, and two compounds, 4b and 4d, were found to be new lead molecules targeting PIK3CA [Display omitted] [ABSTRACT FROM AUTHOR]

• APTT was synthesized and fully characterized by FT-IR, 1H-NMR, 13C-NMR, ESI-MS and single-crystal X-ray diffraction. • Structural, topological and electronic proprieties of APTT were studied by B3LYP/6-311++G** calculations. • Complete assignments of vibration modes are reported. • Good concordances there are between experimental spectra and predicted geometrical parameters. • APTT was evaluated in vitro for their antihyperglycemic activity. In this work, 1,2,4-triazole derivative derived from Isoniazid namely, 4-amino-5-(pyridin-4-yl)-4H-1,2,4-triazole-3-thiol (APTT) was synthesized and fully characterized by FT-IR, 1H NMR, 13C NMR, HRMS-ESI, and single crystal X-ray diffraction. The optimized structures of monomer, dimer and tetramer of APTT with the hybrid B3LYP/6-311++G** method explain the inter and intra-molecular interactions observed experimentally by X-ray diffraction. The presence of tetramer justify the strong IR bands observed in the 2400 and 1800 cm-1 region. The IR spectrum was completely assigned and the scaled force constants reported by using the scaled quantum mechanical force field (SQMFF) approach and the Molvib program. Good correlations between experimental and predicted NMR and UV-Vis spectra are obtained. Both NBO and AIM calculations reveal the inter and intra-molecular interactions and the low stability of APTT in solution while the gap values suggest its low reactivity in the same medium. The different studies reveal the important role of intra and inter-molecular interactions in the stability and reactivity of APTT in the two media. Also, antimicrobial activity of APTT was evaluated against common bacteria and fungi as S. aureus, S. pyrogenes, E. faecalis, V. parahaemolyticus, P. aeruginosa, S. enteritidis, S. cerevisiae, C. albicans, C. tropicalis, C. glabrata , and C. parasilosis. The antimicrobial activity results showed that APTT exhibited both bactericidal and fungicidal activity against all the microbial strains tested. These two effects underline the versatility of the title compound in combating a broad spectrum of microbial infections. [ABSTRACT FROM AUTHOR]

• A variety of pyrimidinyl oxa/thia/triazoles are prepared using trimethylsilyl isothiocyanate. • Docking results indicated that the compounds 3e, 5e, 7a have better docking scores than Chloramphenicol. • The compounds 3e, 5a, 5e have better docking scores than Fluconazole. • The unsubstituted, methyl and nitro substituted molecules showed greater antimicrobial activity. Organosilicon reagent-trimethylsilyl isothiocyanate, a common reagent for the development of 1,3,4-oxadiazoles, 1,3,4-thiadiazoles and 1,2,4-triazoles was reported by the reaction with heteroaromatic acid hydrazides under conventional and ultrasonication methodologies in a polar protic solvent, ethanol under appropriate conditions. Molecular docking studies were performed with the X-ray crystal structures of the target molecules (PDB ID: 2w9s and PDB ID: 6f0e). The docking results indicated that H-bond interactions and hydrophobic interactions were responsible for the inhibition of protein. All 15 synthesized molecules showed excellent binding energy than the standard drugs. The compounds 3a, 3b, 3e, 5a, 5b, 5e and 7a exhibited low MIC values against S. aureus whereas 3a, 3b, 5a, 5b and 7a against B. subtilis. The compounds 5a, and 5b also displayed low MIC values against P. aeruginosa. The MBC of these compounds is 2×MIC, and is equal to standard drug, Chloramphenicol. The compounds 3a, 3b, 3e, 5a, 5b, 5d and 5e showed low MIC values against A. niger whereas 3a, 5a, 5b, 7a, 7b and 7e against P. Chrysogenum. The MFC is 2×MIC and is equal to standard drug, Fluconazole. The structure-activity relationship of the compounds revealed that unsubstituted, methyl and nitro substituted compounds showed greater antimicrobial activity than those with chloro and bromo substituents. [Display omitted] [Display omitted] [ABSTRACT FROM AUTHOR]

• A new series of isatin based 1,2,3-triazole hybrids was designed, synthesized and evaluated for antimicrobial activity. • The structure of isatin linked terminal alkyne (2) was established by single crystal X-ray crystallography. • Amongst the synthesized compounds, 5d exhibited highest potency towards the tested fungal strains C. albicans and A. niger with equivalent MIC of 0.0057 μmol/mL. • Molecular docking, molecular dynamics, MM/PBSA and ADME studies were also performed. With the aim to identify new antimicrobials, in the present study a new series of isatin based 1,2,3-triazoles (5a-5f & 6a-6f) has been synthesized through CuAAC click reaction and characterized by FTIR, NMR and MS spectral methods. In vitro antimicrobial assay suggested that synthesized derivatives exhibited good to high efficacy against tested microorganisms. Compounds 5c, 5d, 5f exhibited promising potency towards E. coli , similarly, 5b, 5d, 5e and 6d displayed good antifungal efficacy against C. albicans. These compounds also exhibited better potency against both the fungal strains as compared to the standard drug. Molecular docking studies of these derivatives performed against antibacterial and antifungal targets 1KZN (E. coli) and 5TZ1 (C. albicans) revealed that hybrid 5b possessed lowest binding energy i.e. -9.1 kcal/mol and -11.0 kcal/mol, respectively. Moreover, Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) analysis was used to compute the various components contributing to binding free energy of 5b with these biological targets. [Display omitted] [ABSTRACT FROM AUTHOR]

Life-threatening invasive fungal infections pose a serious threat to human health. A series of novel triazole derivatives bearing a pyrazole-methoxyl moiety were designed and synthesized in an effort to obtain antifungals with potent, broad-spectrum activity that are less susceptible to resistance. Most of these compounds exhibited moderate to excellent in vitro antifungal activities against Candida albicans SC5314 and 10,231, Cryptococcus neoformans 32,609, Candida glabrata 537 and Candida parapsilosis 22,019 with minimum inhibitory concentration (MIC) values of ≤0.125 μg/mL to 0.5 μg/mL. Use of recombinant Saccharomyces cerevisiae strains showed compounds 7 and 10 overcame the overexpression and resistant-related mutations in ERG11 of S. cerevisae and several pathogenic Candida spp. Despite being substrates of the C. albicans and Candida auris Cdr1 drug efflux pumps, compounds 7 and 10 showed moderate potency against five fluconazole (FCZ)-resistant fungi with MIC values from 2.0 μg/mL to 16.0 μg/mL. Growth kinetics confirmed compounds 7 and 10 had much stronger fungistatic activity than FCZ. For C. albicans , compounds 7 and 10 inhibited the yeast-to-hyphae transition, biofilm formation and destroyed mature biofilm more effectively than FCZ. Preliminary mechanism of action studies showed compounds 7 and 10 blocked the ergosterol biosynthesis pathway at Erg11, ultimately leading to cell membrane disruption. Further investigation of these novel triazole derivatives is also warranted by their predicted ADMET properties and low cytotoxicity. In this study, twenty-nine novel triazole derivatives bearing pyrazole-methoxyl side chains were designed and synthesized based on our previous work. Most compounds exhibited moderated to excellent in vitro antifungal activities against Candida albicans SC5314 and 10,231, Cryptococcus neoformans 32,609, Candida glabrata 537 and Candida parapsilosis 22,019 with minimum inhibitory concentration (MIC) values of ≤0.125 μg/mL to 0.5 μg/mL. Among them, representative compounds 7 and 10 displayed broad-spectrum inhibitory effect against seven human pathogenic fungi, two fluconazole-resistant C. albicans and three muti-drug resistant Candida auris isolates. Importantly, by using of the recombinant Saccharomyces cerevisiae strains, we revealed that compounds 7 and 10 overcame the overexpression or the resistant-related mutations in ERG11 in the pathogenic Candida spp. Time-growth studies confirmed that the highly active compounds 7 and 10 had better fungistatic activity than FCZ. Moreover, compounds 7 and 10 effectively inhibited yeast-to-hyphae transition and biofilm formation, and destroyed the mature biofilm. Preliminary mechanism of action studies indicated that our synthesized compounds acted on the ergosterol biosynthesis pathway via inhibition of fungal Erg11, ultimately leading to cell membrane disruption. Collectively, the above findings implied that these novel triazole derivatives with more effective, proper ADMET properties and low cytotoxicity can contribute to overcome antifungal resistance and warrant further investigation. [Display omitted] • Most of target compounds exhibited moderated to excellent activity against C. albicans , C. neoformans , C. glabrata and C. parapsilosis. • Compounds 7 and 10 displayed broad-spectrum inhibitory effect against tested pathogenic fungi. • Compounds 7 and 10 overcame the overexpression or the resistant-related mutations in ERG11 in the pathogenic Candida spp. • Compounds 7 and 10 effectively inhibited yeast-to-hyphae transition and biofilm formation, and destroyed the mature biofilm. • Compounds 7 and 10 blocked the ergosterol biosynthesis pathway at Erg11, ultimately leading to cell membrane disruption. [ABSTRACT FROM AUTHOR]

A new series of thiazolidine-2,4-dione tethered 1,2,3-triazole derivatives were designed, synthesized and screened for their α-amylase inhibitory potential employing in vitro and in silico approaches. The target compounds were synthesized with the help of Cu (I) catalyzed [3 + 2] cycloaddition of terminal alkyne with numerous azides, followed by unambiguously characterizing the structure by employing various spectroscopic approaches. The synthesized derivatives were assessed for their in vitro α-amylase inhibition and it was found that thiazolidine-2,4-dione derivatives 6e , 6j , 6o , 6u and 6x exhibited comparable inhibition with the standard drug acarbose. The compound 6e with a 7-chloroquinolinyl substituent on the triazole ring exhibited significant inhibition potential with IC 50 value of 0.040 μmol mL−1 whereas compound 6c (IC 50 = 0.099 μmol mL−1) and 6h (IC 50 = 0.098 μmol mL−1) were poor inhibitors. QSAR studies revealed the positively correlating descriptors that aid in the design of novel compounds. Molecular docking was performed to investigate the binding interactions with the active site of the biological receptor and the stability of the complex over a period of 100 ns was examined using molecular dynamics studies. The physiochemical properties and drug-likeliness behavior of the potent derivatives were investigated by carrying out the ADMET studies. [Display omitted] • Thiazolidine-2,4-dione tethered 1,2,3-triazoles were designed and synthesized. • Derivatives exhibited α-amylase inhibition comparable to acarbose. • QSAR established quantitative relationship between structures and activities. • Molecular docking and dynamics unveil binding interactions and complex stability. • Descriptors IDDE, GGI6, and L3s were positively correlated with activity. [ABSTRACT FROM AUTHOR]

The triazole functional group plays a pivotal role in the composition of biomolecules with potent anticancer activities, including numerous clinically approved drugs. The strategic utilization of the triazole fragment in the rational modification of lead compounds has demonstrated its ability to improve anticancer activities, enhance selectivity, optimize pharmacokinetic properties, and overcome resistance. There has been significant interest in triazole-containing hybrids in recent years due to their remarkable anticancer potential. However, previous reviews on triazoles in cancer treatment have failed to provide tailored design strategies specific to these compounds. Herein, we present an overview of design strategies encompassing a structure-modification approach for incorporating triazoles into hybrid molecules. This review offers valuable references and briefly introduces the synthesis of triazole derivatives, thereby paving the way for further research and advancements in the field of effective and targeted anticancer therapies. [Display omitted] • Emphasizing structure-modification approaches of triazoles as anticancer pharmacophores or versatile linkers. • Providing valuable insight into the role of triazoles as versatile linkers in degraders, PDCs, ADCs and anticancer agents. • Summarizing the synthesis methods for 1,2,3-triazoles and 1,2,4-triazoles based on various substitutions. [ABSTRACT FROM AUTHOR]

[Display omitted] • New 1,2,3-triazole derivatives based on 4-Chlorobenzenesulfonyl were synthesized. • Antioxidant activities of the compounds using DPPH, ABTS and CUPRAC methods. • Cholinesterase (AChE and BuChE) inhibition activity of the compounds, • The anticancer properties against Caco-2 and PC3 cancer cell lines were investigated. • Detailed ADMET analyses of hybrid structures and molecular docking studies supported results. New hybrid structures containing 4-chlorosulfonamide and 1,2,3-triazole units were designed and synthesized. Antioxidant, cholinesterase (AChE and BuChE) and anticancer activities of these hybrid structures were investigated. Especially the DPPH activity of compound 8a (IC 50 : 8.659 μg/mL) was found to be higher than ascorbic acid (IC 50 : 4.780 μg/mL), α-Tocopherol (IC 50 : 9.229 μg/mL) and BHT (IC 50 : 7.948 μg/mL). Compounds 8d, 8 g and 8b also had good activity values. The anticancer activities of the hybrid structures were determined using PC3 (prostate cancer) and Caco-2 (colon adenocarcinoma) cell lines. 5-Fu (IC 50 : 4.34 ± 1.29) was used as standard. Compounds 8c (IC 50 : 3.82 ± 1.86 µM) for PC3 and 8 h (IC50: 6.39 ± 1.14 µM) for Caco-2 were found to have outstanding activity values. All synthesized compounds' AChE and BuChE inhibitory activities were determined using Galantamine as a standard. Especially 8b (IC50: 0.29 ± 0.003 mM) had about 28 times better activity than the standard Galantamine (IC 50 : 8 ± 0.05 mM). After a thorough examination, the ADMET properties of the molecules were found to meet the rigorous standards required for pharmaceutical applicability. Furthermore, their impressive oral absorption capability is linked to their ability to effectively navigate the blood–brain barrier and the gastrointestinal tract. In-vitro evaluations were further validated through molecular docking studies conducted in silico. [ABSTRACT FROM AUTHOR]

• New triazole derivatives were synthesized as antifungal agents. • MIC 50 values were observed against C. albicans strain 4c, 4f and 4 g. • Compound 4c showed the same MIC 50 value as fluconazole used as reference drugs. Fungal infections pose a significant threat to both morbidity and mortality, especially in immunocompromised patients, notably those with conditions such as AIDS. In the last two decades, the incidence of such fungal infections has increased significantly, especially due to Candida species. The increasing incidence of life-threatening fungal infections has increased the need for new drugs to treat these infections. In this study, 10 novel oxadiazole-triazole hybrid compounds were synthesized. Analysis of the obtained compounds provided by 1H NMR (proton nuclear magnetic resonance), 13C NMR (carbon nuclear magnetic resonance) spectroscopic methods and HRMS (high resolution mass spectrometry) spectrometric method. The inhibition effects of the obtained compounds on the 14α-demethylase enzyme were investigated. Among the synthesized compounds, 4a (contains 4-methyl substituent), 4c (contains 4-cyano substituent), 4d (contains 4-nitro substituent), 4e (contains 4-fluoro substituent), 4 g (contains 4‑bromo substituent) and 4j (contains 3,4-dichloro substituent) coded compounds were useful against C. parapsilosis strain; Compounds 4c, 4f and 4 g also showed significant inhibitory effect against C. albicans strain. Within the scope of the study, the interactions of 14α-demethylase enzyme active site and our compound were elucidated by molecular modeling and molecular dynamics studies. Binding points were determined by docking studies for the selected compounds in enzyme active site. The strongest interaction with 14α-demethylase enzyme active sites was observed in 4c and 4 g coded compounds. [ABSTRACT FROM AUTHOR]

Owing to the biological importance of 1,2,3-triazoles and benzoxazine-3(4H)-ones scaffolds, we have attempted to design and synthesize novel 1,2,3-traizoles linked to benzoxazin-3-one moiety. Indeed, a novel series of 1,4-disubstituted 1,2,3-triazoles containing 2H-1,4-benzoxazin- 3-(4H)-one were synthesized. The 1,2,3-triazoles were obtained in high yields by a double copper-catalyzed azide-alkyne click chemistry reaction between azides and corresponding propargylated benzoxazin-3-ones. These compounds incorporate both the 2H-benzo[b] (Rao et al., 2019; Fringuelli et al., 2009) [1,4]oxazin-3-one motif and two 1,2,3-triazole heterocycles. The synthesized molecules were characterized by spectroscopic techniques such 1H NMR, 13C NMR, FT-IR and elemental analysis. [Display omitted] • Developed a synthetic route for new 2H-benzo[b] [1,4]oxazin-3-one derivatives. • Utilized click chemistry to incorporate 1,2,3-triazole moieties. • Demonstrated efficient and regioselective formation of 1,2,3-triazoles. • High yield and purity of the synthesized compounds. • Comprehensive characterization of the new derivatives using NMR, IR, and elemental analysis. [ABSTRACT FROM AUTHOR]

• A novel series of thiazolidinone based 1,2,3-triazole derivatives were designed, synthesized, and evaluated for their cytotoxic activity. • Anti-proliferative activity was assessed against HT-1080, A-549, MCF-7 and MDA-MB-231 cells lines. • Hybrid compounds 14b and 14d showed important inhibitory activity against HT-1080 and A-549 cancer cell lines with an IC 50 value of 18 μM. • Binding modes of all compounds were identified via molecular docking. • Compounds 14b and 14d had higher affinity for Bcl-2 as compared to other compounds. A novel series of thiazolidinone based 1,2,3-triazole derivatives were designed, synthesized, and evaluated for their cytotoxic activity against four human cancer cell lines, including fibrosarcoma (HT-1080), lung carcinoma (A-549), and breast carcinoma (MCF-7 and MDA-MB-231). NMR (1H and 13C) and HRMS established the newly synthesized compounds' structural identification and molecular weight. Most synthesized compounds displayed moderate cytotoxic activity, with IC 50 values from 20 to 40 μM. Furthermore, hybrid compounds 14b and 14d showed important inhibitory activity against HT-1080 and A-549 cancer cell lines with an IC 50 value of 18 μM. Molecular docking analyses also confirmed a higher binding affinity of compounds 14a-e , as compared to Doxorubicin (control), towards Bcl-2 protein. In particular, compounds 14b and 14d had higher affinity for Bcl-2 as compared to other compounds. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • Synthesis of (E)-4-(4-(dimethylamino)benzylideneamino)-5-(pyridin-4-yl)-2 H -1,2,4-triazole-3(4 H)-thione (DPT). • Analysis of anticorrosion property of DPT on C1018 carbon steel by various electrochemical and theoretical techniques. • Confirmation of the formation of protective film of DPT on the surface of carbon steel by SEM-EDX and XPS studies. • Verification of experimental data with Quantum chemical parameter obtained from DFT, and Monte Carlo simulation studies. A new triazole derivative, (E)-4-(4-(dimethylamino)benzylideneamino)-5-(pyridin-4-yl)-2 H -1,2,4-triazole-3(4 H)-thione (DPT), was synthesized and characterized using spectral data. The electrochemical experimental techniques were utilized to evaluate the inhibition efficiency (IE) of DPT for the corrosion of C1018 carbon steel. The studies revealed that, DPT is highly efficient with IE value 90% at 250 ppm. Further, the addition of DPT resulted in the decrease of cathodic as well as anodic current densities which is the indication of mixed-type inhibition. Also, the studies inferred the Langmuir model for DPT-metal adsorption. The surface morphological studies of C1018 carbon steel with and without DPT was investigated using SEM, EDX, and XPS, which indicated the strong adsorption of metal-DPT. Monte-Carlo simulation and Density functional theory approaches had been employed for correlating the structure of DPT and its corrosion inhibition ability. The high IE values of DPT observed in experimental studies were in agreement with the theoretical studies, and hence DPT acts as good inhibitor for the corrosion of C1018 steel. [ABSTRACT FROM AUTHOR]

In this paper, the inulin derivative (3) bearing 1,2,3-triazole and diphenyl phosphate was successfully synthesized by CuAAC Click chemistry. Detailed structural characterization was determined using FTIR spectroscopy, 1H NMR spectroscopy, 13C NMR spectroscopy, and elemental analysis. The antioxidant activities against hydroxyl radicals, superoxide radicals, and DPPH radicals were estimated in vitro respectively. The results showed that the antioxidant activity of the inulin derivative (3) was significantly enhanced compared with inulin. The inulin derivative (3) exhibited stronger radical scavenging abilities, especially against hydroxyl radicals and superoxide radicals. The scavenging values of the inulin derivative (3) were 98.2% and 95.4% at 1.6 mg/mL against hydroxyl radicals and superoxide radicals respectively. Besides, the scavenging value of the inulin derivative (3) increased by about 40% to scavenge DPPH radicals at 1.6 mg/mL than inulin. The results showed that the inulin derivative (3) bearing 1,2,3-triazole and diphenyl phosphate exhibited tremendously enhanced antioxidant activity compared with inulin. The synthetic strategy might provide an effective way to prepare novel inulin antioxidant biomaterials. • The inulin derivative bearing 1,2,3-triazole and diphenyl phosphate was successfully synthesized. • Detailed structural characterization of the inulin derivative was carried out. • The inulin derivative showed significantly enhanced antioxidant activity. • The functional groups 1,2,3-triazole and diphenyl phosphate were the key factors to improve the antioxidant activity. [ABSTRACT FROM AUTHOR]

Substitution of chloride by azide in cyclometalated 5-R-1,3-di(2-pyridyl)-benzene platinum(II) complexes (R = mesityl, methyl or 2-thienyl) leads to novel azido complexes with an intense phosphorescence that is modulated by the nature of R. An increase of the concentration brings about to the formation of aggregates with a red-shifted emission. Furthermore, the presence of the ancillary azido group allows, via i -click reaction, the obtainment of even more emissive 1,2,3-triazole derivatives. The 1,2,3-triazolate of the mesityl and 2-thienyl N^C^N–Pt(II) complexes were characterized by X-ray diffraction analysis and their photophysical properties were deeply investigated. [Display omitted] • Synthesis of novel NCN-Pt(II) complexes and their azido and triazole derivatives via i -click reaction. • The photophysical properties of the new NCN-Pt(II) derivatives were deeply investigated obtaining excellent quantum yields. • Density Functional Theory (DFT) and Time Dependent DFT (TDDFT) calculations have been carried out. • X-ray structure has been determined to confirm the proposed structures of the triazole derivatives. [ABSTRACT FROM AUTHOR]

[Display omitted] • XGBoost emerged as the best predictor. • ML approach shows high CIE values for Triazole compounds. • DFT calculations assume a pivotal role within the QSPR model. This paper endeavors to present an in-depth investigation into the corrosion inhibition efficiency (CIE) of novel triazole derivatives serving as corrosion inhibitors. Among the array of models considered, the extreme gradient boosting (XGBoost) model emerged as the most adept predictor in forecasting the CIE of N -heterocyclic organic compounds. This resolute preference for the XGBoost model was consistently upheld when employed in the prediction of the CIE for three newly synthesized triazole derivatives, namely, 2-[5-Phenyl-1-(2′-furanylmethylene)imino-(1,3,4)homotriazole]thio-N-(2′-furanyl)hypomethylacetylhydrazine, 2-[5-(3′-Methyl)Phenyl-1-(2′-furanylidine)imino-(1,3,4)homotriazole]thio-N-(2′-furanylidine) acetylhydrazine, and 2-[5-(4′-Methyl)Phenyl-1-(2′-furanylidine)imino-(1,3,4)homotriazole]thio-N-(2′-furanylidine) acetylhydrazine. Remarkably, this application of the XGBoost model yielded notably elevated CIE values, spanning from 88.35 % to 93.41 %. Supplementary density functional theory (DFT) calculations for these derivative compounds further substantiated the predictive trends observed through machine learning and experimental predictions. These calculations revealed robust adsorption energies falling within the range of −17.95 to −19.76 eV, in alignment with the CIE trends established through the machine learning framework. [ABSTRACT FROM AUTHOR]

• To simulate the marine environment, a 3.5 wt.% NaCl solution was used as the corrosive medium. • An efficient corrosion inhibitor for copper in NaCl (STR) has been synthesized. • The corrosion inhibition behavior of STR and BTA on pure copper was investigated. • Nitrogen atoms are the main adsorption sites for STR and BTA. • Theoretical studies have been performed to understand the adsorption mechanism. Quantum chemical calculations clearly support the behavior of STR and BTA adsorbed on the copper surface. The present study investigates the effectiveness of a novel inhibitor, 2‑hydroxy-5-((4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl)methyl) benzaldehyde (STR), in preventing copper from corrosion in a 3.5 wt.% NaCl solution. A comparative study of the inhibition efficiency between our newly synthesized water-soluble triazole STR, and the commercially available Benzotriazole (BTA) was evaluated using electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization (PDP) tests. The results revealed a substantial reduction in the rate of copper oxidation with increasing inhibitor concentrations. At 10−3 M, STR and BTA demonstrated inhibition efficiencies of 92.73% and 97.62% respectively. Analysis of the Tafel curves showed that the inhibitors used exhibited mixed type behavior. Langmuir isotherms showed that the STR and BTA molecules are adsorbed on copper surface, following the chemical adsorption process. Theoretical calculations based on density functional theory (DFT) method and molecular dynamic (MDS) simulations, provided valuable insights into the efficacy and mode of action of STR and BTA as copper corrosion inhibitors in a 3.5 wt.% NaCl solution. [Display omitted] [ABSTRACT FROM AUTHOR]

• Solvation free energies can be explored by employing various solvents. • The FT-IR, FT-Raman, NMR and Mass spectra studies was performed. • Molecular descriptors for identifying the most reactive bioactive Triazole derivative. • Simulations of molecular dynamics (MD) and docking are used to predict pharmacological properties. In the present study, (E)-3-(2-(4-amino-5-mercapto-4H-1,2,4-triazol-3-yl)hydrazono)methyl)-2-bromo-6-methoxyphenol (AMTMP) is synthesized and characterized utilizing FT-IR, FT-Raman, NMR, Mass Spectra, and vibrational modes at DFT/B3LYP/6-31G (d, p) computational studies. The calculated properties were subsequently compared to the results of experiments. The absorption characteristics were assessed through the utilization of various kinds of solvents. The molecular properties of AMTMP, including the natural bond orbital (NBO), molecular electrostatic potential (MEP), and local and global reactivity descriptors, were utilized to ascertain the stability, reactivity, and reactive sites on the molecule. Using molecular docking, we have investigated the AMTMP's affinity for CA-2 as well as its potential binding mode. For the purpose of assessing the stability of AMTMP-CA-2 complexes over time, MD simulations were performed. The results suggest that AMTMP could act as CA-2 inhibitor for targeting GSC in GBM. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • Combination of experiments and DFT calculations. • Triazole derivatives are eco-friendly and sustainable inhibitors for metal. • Effect of various derivative groups on inhibition efficiency. • Multi-angle study of molecular activity and adsorption behavior on Cu surface. • Provide reference for the selection of organic inhibitors for multiple metals. The impact of triazole derivative groups on corrosion inhibition performance of copper (Cu) film is studied by using 3-amino-1,2,4-triazole-5-carboxylicacid (ATA-O), 1H-1,2,4-triazole-3,5-diamine (ATA-N) and 3-amino-5-mercapto-1,2,4-triazole (ATA-S) as environment-friendly inhibitors. Electrochemical analysis showed that anti-corrosion passivation layer is formed on Cu surface after adding inhibitors with high inhibition efficiency of 54 %, 87 % and 98 % respectively, and improve the surface quality which is verified by atomic force microscope (AFM) and scanning electron microscopy (SEM) tests. Such results are consisted with static etch experiments. The mechanism of corrosion inhibition was revealed by theoretical calculation, which prove that the lone electron pair in empty orbitals of the O, N, S atoms on inhibitors hybridize with the Cu-d orbital to form covalent bonds and enhance the adsorption passivation action. Such study dissects the reasons for the potent inhibitory effect of triazole derivatives at the atomic level, and provides new method for efficient selection of inhibitors. [ABSTRACT FROM AUTHOR]

• Synthesis of triazole and their Derivatives. • Synthesis of triazole by refluxing Method, microwave Method, Ultrasound, metal catalyst. • Biological applications of triazole derivatives Anticancer, Antibacterial, Antifungal, antiviral. The triazole scaffold is a key element in heterocyclic chemistry, giving a fundamental building block in organic, medicinal chemistry, and material science. Triazole composed of a 5-membered heterocyclic ring with three N-atoms and two double bonds. Triazole fragment exhibits favourable bioavailability, facilitating the synthesis of wide range of compounds with excellent biological importance. Decades of research highlights the therapeutic potential, such as antibacterial, anti-inflammatory, cytotoxic, antitumor, and analgesic effects. This review focuses (2013–2023) on recent advancement in the synthesis of triazole derivatives from different nitrogen sources, and displaying their biological functions, structural modification, and bioavailability, emphasizing the importance of N-containing heterocycles in pharmaceuticals and sensing. Researchers, especially those who focused on the development of triazole derivatives with anticancer, antibacterial, antifungal, antitubercular and antiviral properties, will find this review is highly significant. [Display omitted] [ABSTRACT FROM AUTHOR]

As one of the most promising biopolymers for a variety of potential applications, chitosan has attracted much attention because of its unique biological, chemical, and physical properties. The functionalization of chitosan has been adopted to synthesize novel chitosan derivatives with improved water-solubility and excellent biological activities. In this paper, chitosan was functionalized with a triphenylphosphonium group by means of the copper (I) catalyzed azide-alkyne "click" reaction and has been investigated as potential polymer for agricultural antifungal biomaterial. The influence of chemical modification on the structural characteristics and water-solubility of chitosan was investigated by FTIR spectroscopy, 1H NMR spectroscopy, elemental analysis, and UV–vis spectrum. Furthermore, the antifungal property of target chitosan derivative against four plant threatening fungal pathogens was evaluated and in vitro investigation demonstrated that triphenylphosphonium salt incorporated chitosan backbone had excellent antifungal property compared with chitosan and intermediate chitosan derivative. Notably, target chitosan derivative displayed relatively strongest antifungal effect with over 80% inhibitory index against Botrytis cinerea at 1.0 mg/mL. The results of a detailed antifungal study indicated that cationic chitosan derivative bearing 1,2,3-triazole and triphenylphosphonium moieties provided a promising platform for preparation of novel cationic antifungal biomaterials in the field of agriculture. [ABSTRACT FROM AUTHOR]

• The inhibition effectiveness of nitrogen-containing organics on copper was proved. • Triazole derivatives have better anti-corrosion performance at low concentration. • DFT and MD simulation provide support for the experimental results. Corrosion inhibitors are added to the slurry to mitigate the excessive corrosion of copper in the chemical mechanical polishing (CMP) process, and their adsorption mechanisms will affect the corresponding inhibition efficiencies. A comprehensive study of several types of inhibitors in the weak alkaline H 2 O 2 -sarcosine solution found that the number of heteroatoms and the substitution behavior of amino groups in nitrogen-containing organics could improve their corrosion inhibition efficiencies. The electrochemical results showed that all the inhibitors were mixed-type except for BIT, which was an anodic inhibitor. The benzo derivatives could not provide favorable inhibition at low concentrations, while the triazole derivatives are free from this deficiency. When 0.5 wt% inhibitors were added to the blank solution respectively, the corrosion inhibition performances of benzo derivatives ranked as IND < BZA < BIT, and the order of inhibition efficiencies of triazole derivatives is TAZ < 3-ATA < 5-ATZ. The SEM images of the polished wafer surfaces coincided with electrochemical experiments. Quantum chemical calculations predicted the reactive sites of molecules. Molecular dynamics simulations showed that triazole inhibitors could be adsorbed in parallel in the aqueous environment, while the benzo inhibitor molecules presented a certain tilt with the Cu (1 1 1) surface. [ABSTRACT FROM AUTHOR]

• Synthesis and crystallization of novel FPTT compound. • Structure of FPTT is determined by SC-XRD, supported by 1H NMR, 13C NMR, FTIR, UV-vis techniques. • DFT studies of the compound to validate the structural and electronic properties. • Molecular docking studies for good binding affinity. • ADMET for drug likeness. One of the most significant issues in contemporary medicine and pharmacy is the search for powerful bioactive, efficient, low-toxic anti-COVID agents. In this contrast, present work involves the synthesis of triazole derivative 6-(4-Flurophenyl)-3-(pyridine-4yl)-7H-(1,2,4)triazolo(3,4-b) (1,3,4)thiadiazine (FPTT) and its characterizations using various spectroscopic techniques (LCMS, NMR, UV-vis, FTIR). The vibrational wavenumbers were evaluated and found to be in good agreement with theoretical values. The crystal structure is determined using single crystal X-ray diffraction study and the structure is reinforced by several intra-, intermolecular and π ··· π interactions. These interactions result in the formation of R 1 2 (7), R 3 3 (17), S(5) and S(6) synthons which significantly contribute towards the stability of the crystal structure. Further, these interactions are validated through Hirshfeld surface and 2D fingerprint plot analysis. The C-H···N and H···H contacts are the major contributors and are in consistency with the topology and natural bond orbital results. The optimized geometrical parameters through density functional theory (DFT) are in good agreement with the experimental data. Further, various electronic properties of the compound were evaluated using the optimized structure. The molecular electrostatic potential map (MEP) and Fukui function analysis revealed the most active sites. Analysis of non-covalent interactions based on a gradient of reduced density revealed the presence of van der Waals interactions. Intrigued, by the presence of large amounts of non-covalent interactions the pharmacokinetic profiles of the compound were evaluated through ADMET provides an insight into potential inhibitors and novel drug candidates. Further in-silico studies such as molecular docking was carried out against the Omicron variant of SARS-CoV-2 spike protein with an intention to assist towards the production of improved vaccines and therapeutics. [Display omitted] [ABSTRACT FROM AUTHOR]

In this work, we utilized the molecular hybridization strategy to design and synthesize novel 1,2,3-triazole benzothiazole derivatives K1-26. The antiproliferative activities against MGC-803, Kyse30 and HCT-116 cells were explored, and their structure-activity relationship were preliminarily conducted and summarized. Among them, compound K18 , exhibited the strongest proliferation inhibitory activity, with esophageal cancer cells Kyse30 and EC-109 being the most sensitive to its effects (IC 50 values were 0.042 and 0.038 μM, respectively). Compound K18 effectively inhibited tubulin polymerization (IC 50 = 0.446 μM), thereby hindering tubulin polymerize into filamentous microtubules in Kyse30 and EC-109 cells. Additionally, compound K18 induced the degradation of oncogenic protein YAP via the UPS pathway. Based on these dual molecular-level effects, compound K18 could induce G2/M phase arrest and cell apoptosis in Kyse30 and EC-109 cells, as well as regulate the expression levels of cell cycle and apoptosis-related proteins. In summary, our findings highlight a novel 1,2,3-triazole benzothiazole derivative K18 , which possesses significant potential for treating esophageal cancers. [Display omitted] • Compound K18 showed low nanomolar IC 50 values of 0.042 and 0.038 μM against Kyse30 and EC-109 cells. • Compound K18 inhibited tubulin polymerization (EC 50 = 0.445 μM). • Compound K18 induced YAP degradation. • Compound K18 induced the G2/M phase arrest and apoptosis in Kyse30 and EC-109 cells. [ABSTRACT FROM AUTHOR]

The Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP1) is a convergent node for oncogenic cell-signaling cascades. Consequently, SHP1 represents a potential target for drug development in cancer treatment. The development of efficient methods for rapidly tracing and modulating the SHP1 activity in complex biological systems is of considerable significance for advancing the integration of diagnosis and treatment of the related disease. Thus, we designed and synthesized a series of imidazo[1,2,4] triazole derivatives containing salicylic acid to explore novel scaffolds with inhibitory activities and good fluorescence properties for SHP1. The photophysical properties and inhibitory activities of these imidazo[1,2,4] triazole derivatives (5a-5y) against SHP1PTP were thoroughly studied from the theoretical simulation and experimental application aspects. The representative compound 5p exhibited remarkable fluorescence response (P: 0.002) with fluorescence quantum yield (QY) of 0.37 and inhibitory rate of 85.21 ± 5.17% against SHP1PTP at the concentration of 100 μM. Furthermore, compound 5p showed obvious aggregation caused quenching (ACQ) effect and had high selectivity for Fe3+ ions, good anti-interference and relatively low detection limit (5.55 μM). Finally, the cellular imaging test of compound 5p also exhibited good biocompatibility and certain potential biological imaging application. This study provides a potential way to develop molecules with fluorescent properties and bioactivities for SHP1. [Display omitted] • Compound 5p was a fluorescent molecule with good quantum yield and inhibitory activity against SHP1. • The inhibitory activity of compound 5p obviously related with fluorescence response. • The activity of SHP1 enzyme could be adjusted effectively by binding capability of compound 5p to Fe3+. [ABSTRACT FROM AUTHOR]

[Display omitted] • Ru(II), Rh(III), Ir(I/III), Pt(II), and Pd(II) complexes of nitron were determined the cytotoxic effects. • Cancer cell lines, namely HeLa, MDA-MB-231, PC3 and a normal line CCD-34Lu were used. • Ru-nitron and Rh-nitron complexes were exhibited extraordinary cytotoxic effect. • Flow cytometry, stability/aquation, and FS-DNA interaction experiments were performed. This investigation scrutinizes the cytotoxic properties inherent in nitron metal complexes, a commercially available 1,2,4-triazole derivative. The study assesses the anticancer potential of ruthenium(II) (1), rhodium(III) (2), iridium(I/III) (3 and 5), palladium(II) (4), and platinum(II) (6) complexes of nitron by subjecting them to examination as agents against cancer cell lines, namely HeLa, MDA-MB-231, PC3, and non-cancerous CCD-34Lu cells. Results derived from the MTT assay substantiate that each nitron complex manifests cytotoxic activity against a spectrum of cancer cells. Notably, the ruthenium (Ru) and rhodium (Rh) complexes exhibit pronounced cytotoxic effects on cancer cells, suggesting their potential as impactful chemotherapeutic agents. Flow cytometry studies further reveal a predilection of these complexes towards inducing early apoptosis in the target cells. The investigation extends to exploring the stability and aquation dynamics of complex (1), in addition to elucidating the binding model between complex (1) and DNA. [ABSTRACT FROM AUTHOR]

[Display omitted] • New indole-piperazine derivatives were designed and synthesized. • 1,2,3-Triazole incorporated derivatives exhibited significant antiTB activity. • Five 1,2,3-triazole derivatives displayed MIC of 1.6 μg/mL. • Active compounds are non-toxic to the normal cell lines. • Active compounds exhibit high binding affinity target enzymes Inh A and CYP 121. In this report, a library consisting of three sets of indole-piperazine derivatives was designed through the molecular hybridization approach. In total, fifty new hybrid compounds (T1-T50) were synthesized and screened for antitubercular activity against Mycobacterium tuberculosis H37Rv strain (ATCC-27294). Five (T36, T43, T44, T48 and T49) among fifty compounds exhibited significant inhibitory potency with the MIC of 1.6 µg/mL, which is twofold more potent than the standard first-line TB drug Pyrazinamide and equipotent with Isoniazid. N-1,2,3-triazolyl indole-piperazine derivatives displayed improved inhibition activity as compared to the simple and N -benzyl indole-piperazine derivatives. In addition, the observed activity profile of indole-piperazines was similar to standard anti-TB drugs (isoniazid and pyrazinamide) against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa strains, demonstrating the compounds' selectivity towards the Mycobacterium tuberculosis H37Rv strain. All the active anti-TB compounds are proved to be non-toxic (with IC 50 > 300 μg/mL) as verified through the toxicity evaluation against VERO cell lines. Additionally, molecular docking studies against two target enzymes (Inh A and CYP121) were performed to validate the activity profile of indole-piperazine derivatives. Further, in silico-ADME prediction and pharmacokinetic parameters indicated that these compounds have good oral bioavailability. [ABSTRACT FROM AUTHOR]

• Thirteen novel 1,3,4 triazole-benz/thiazole and hydrazide-thiazole derivatives were synthesized and characterized using spectroscopic techniques. • The final compounds were tested against twelve bacterial species and ten fungal pathogens. • The compounds have shown better antifungal activity compared to antibacterial activity. • Compounds 5c, 5d and 5e were studied in-silico for their proposed interaction with lanosterol 14α-demethylase. • Pharmacokinetics properties of the active compounds were also studied. In this work, thirteen new compounds have been synthesized, characterized and evaluated for their antifungal and antimicrobial activities. Seven of them which contain the thiazole ring were obtained by reacting 2-(2-(2-methoxyphenoxy)propanoyl)- N -phenylhydrazine-1-carbothioamide (3) with phenylacyl bromide derivatives, while the other six compounds that have the 1,2,4-triazole ring (6a-6f) were prepared through couple of steps starting from the same intermediate 2-(2-(2-methoxyphenoxy)acetyl)- N -phenylhydrazine-1-carbothioamide (3). All final compounds were characterized using LC-MS, 1H NMR and 13C NMR spectroscopic techniques. All compounds were tested against twelve bacterial strains and ten fungus species. Derivative (5a) that is N '-(3,4-diphenylthiazol-2(3 H)-ylidene)-2(methoxyphenoxy)propanehydrazide had shown the best activity and selectivity toward Yersinia enterocolitica bacterial type. All compounds demonstrated good activity against filamentous fungi species compared to yeast species. Molecular docking studies also showed that derivatives 2-(2-Methoxyphenoxy)- N '-(4-(4-methoxyphenyl)-3-phenylthiazol-2(3 H)-ylidene)propanehydrazide (5c), N '-(4-(4-chlorophenyl)-3-phenylthiazol-2(3 H)-ylidene)-2-(2-methoxyphenoxy)propanehydrazide (5d) and N -(4-(4-fluorophenyl)-3-phenylthiazol-2(3 H)-ylidene)-2-(2-methoxyphenoxy)propanehydrazide (5e) interacted with the active cavity of lanosterol 14α-demethylase enzyme. [Display omitted] [ABSTRACT FROM AUTHOR]

In this study, a series of novel anti-inflammatory compounds with high activity and low toxicity were designed and synthesized based on the natural product pterostilbene skeleton. According to the strategy of pharmacophore combination, we introduced thiazole moiety into pterostilbene skeleton to design and synthesize a novel series of pterostilbene derivatives (a total of 41 compounds), and lipopolysaccharide (LPS)-treated RAW 264.7 cells were screened for anti-inflammatory activity and cytotoxicity. Among them, compound 8 was found to be the most active (against NO: IC 50 = 0.6 μM) compared with pterostilbene and indomethacin. Anti-inflammatory mechanism studies revealed that compound 8 inhibited pro-inflammatory cytokines by blocking the NF-κB/MAPK signaling pathway in LPS-treated RAW 264.7 cells. In vivo experiments showed that compound 8 had a good relieving effect on DSS-induced acute colitis in mice, and also demonstrated a good safety in acute toxicity experiments. In conclusion, compound 8 may be a promising anti-inflammatory lead compound in the treatment of acute colitis. [Display omitted] • Design and synthesis of a series of new pterostilbene derivatives. • Compound D8 inhibits NO secretes by blocking the NF-κB/MAPK signaling pathway in LPS-treated RAW 264.7 cells. • In vivo experiments showed that compound D8 had good safety and therapeutic effect on DSS induced acute colitis in mice. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a well known neurodegenerative disorder alarming millions of people worldwide and the subsequent epidemiological statistics highlights the implication of the disease. AD is a multi-factorial disease, a variety of single-target directed drugs that have reached clinical trials have unsuccessful. Hence, various factors associated without set of AD have been considered in targeted drug discovery and development. Triazoles are five-membered heterocyclic scaffold due to their broad range of biological activities. The present review focuses on the recent developments in the area of medicinal chemistry to explore the diverse chemical structures of potential inhibitors of Alzheimer's disease and also look at its structure-activity relationships (SAR) studies of bioactive compounds for future discovery of suitable drug candidates. The prominence has been given on the major advancements in the medicinal brochure of this pharmacophore for the period during 2012 – 2019. Image 1 • Triazole and its derivatives as showed potent Alzheimer's disease. • Describe the brief SAR of potent compounds. • This review article containing 64 potent triazole derivatives. [ABSTRACT FROM AUTHOR]

Reported herein is the design, synthesis, and pharmacologic evaluation of a class of TRPV1 antagonists constructed on 2,3,4,9-tetrahydro-1 H -pyrido[3,4- b ]indole as A-region and triazole as B-region. The SAR analysis indicated that 2,3,4,9-tetrahydro-1 H -pyrido[3,4- b ]indole analogues displayed excellent antagonism of hTRPV1 activation by capsaicin and showed better potency compared to the corresponding dihydroindole analogues. Optimization of this design led to the eventual identification of 2-((1-(2-(trifluoromethyl)phenyl)-1 H -1,2,3-triazol-4-yl)methyl)-2,3,4,9-tetrahydro-1 H -pyrido[3,4- b ]indole (6g), a potent TRPV1 antagonist. In vitro , using cells expressing recombinant human TRPV1 channels, 6g displayed potent antagonism activated by capsaicin (IC 50 = 0.075 μM) and only partially blocked acid activation of TRPV1. In vivo , 6g exhibited good efficacy in capsaicin-induced and heat-induced pain models and had almost no hyperthermia side-effect. Furthermore, pharmacokinetic studies revealed that compound 6g had a superior oral exposure after oral administration in rats. To understand its binding interactions with the receptor, the docking study of 6g was performed in rTRPV1 model and showed an excellent fit to the binding site. On the basis of its superior profiles, 6g could be considered as the lead candidate for the further development of antinociceptive drugs. Reported herein is the design, synthesis, and pharmacologic evaluation of a class of TRPV1 antagonists constructed on 2,3,4,9-tetrahydro-1 H -pyrido[3,4- b ]indole as A-region and triazole as B-region. Image 1 • Design, synthesis, and pharmacologic evaluation of a class of TRPV1 antagonists which constructed on 2,3,4,9-tetrahydro-1 H -pyrido[3,4- b ]indole as A-region and triazole as B-region. • Optimization of this design led to the eventual identification of 2-((1-(2-(trifluoromethyl)phenyl)-1 H -1,2,3-triazol-4-yl)methyl)-2,3,4,9-tetrahydro-1 H -pyrido[3,4- b ]indole (6g), a potent TRPV1 antagonist. • 6g exhibited potent antagonism activated by capsaicin (IC 50 = 0.075 μM) and only partially blocked acid activation of TRPV1, and demonstrated good efficacy in different pain models and did not elevate core body temperature. [ABSTRACT FROM AUTHOR]

Inhibiting the decomposition of carbohydrates into glucose or promoting glucose conversion is considered to be an effective treatment for type 2 diabetes. Herein, a series of novel xanthone-triazole derivatives were designed, synthesized, and their α-glucosidase inhibitory activities and glucose uptake in HepG2 cells were investigated. Most of the compounds showed better inhibitory activities than the parental compound a (1,3-dihydroxyxanthone, IC 50 = 160.8 μM) and 1-deoxynojirimycin (positive control, IC 50 = 59.5 μM) towards α-glucosidase. Compound 5e was the most potent inhibitor, with IC 50 value of 2.06 μM. The kinetics of enzyme inhibition showed that compounds 5e , 5g , 5h , 6c , 6d , 6g and 6h were noncompetitive inhibitors, and molecular docking results were consistent with the noncompetitive property that these compounds bind to allosteric sites away from the active site (Asp214, Glu276 and Asp349). On the other hand, the glucose uptake assays exhibited that compounds 5e , 6a , 6c and 7g displayed high activities in promoting the glucose uptake. The cytotoxicity assays showed that most compounds were low-toxic to human normal hepatocyte cell line (LO2). These novel xanthone triazole derivatives exhibited dual therapeutic effects of α-glucosidase inhibition and glucose uptake promotion, thus they could be use as antidiabetic agents for developing novel drugs against type 2 diabetes. Image 1 • Twenty-four novel xanthone-triazole derivatives were designed and synthesized. • Xanthone-triazole derivatives significantly increased α-glucosidase inhibition. • 5e , 6a , 6c and 7g had dual effects on α-glycosidase inhibition and glucose uptake. • Most of xanthone-triazole derivatives had low toxicity. [ABSTRACT FROM AUTHOR]

Abstract Needle-like supramolecular structures prepared by the organized aggregation of a 2 H -benzo[ d ][1,2,3]triazole derivative with few-layer graphene using the slow diffusion technique are described. The as-prepared aggregate shows, by using scanning electron microscopy (SEM), the formation of needles with graphene attached on the surface, which was corroborated by Raman spectroscopy and optical microscopy. The graphene-modified aggregate acts as a selective optical waveguide for green light, in contrast to the pristine aggregate which emits green and red light. These new materials may be of crucial importance for the development of high-performance optoelectronic devices. Graphical abstract Image 1 Highlights • Synthesis of 2 H -benzo[ d ][1,2,3]triazole derivative and graphene aggregate to form a new supramolecular assembly. • This aggregate shows properties as optical waveguide. • The graphene-modified aggregate acts as a selective optical waveguide for green light. • These new materials may be of crucial importance for the development of high-performance optoelectronic devices. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Extracellular adenosine 5′-triphosphate (ATP) triggers the P2X7 receptor (P2X7R) ionic channel to stimulate the release of the interleukin-IL-1β cytokine into macrophages. The current study explored the reaction of six structurally diverse triazole derivatives on P2X7-mediated dye uptake into murine peritoneal macrophages. P2X7R activity determined by ATP-evoked fluorescent dye uptake. Triazole derivatives toxicity measured using dextran rhodamine exclusion based colorimetric assay. A740004 and BBG, both P2X7R antagonist, inhibited ATP-induced dye uptake. In contrast, the derivatives 5a , 5b , 5e , and 5f did not diminish P2X7R activity in concentrations until 100 µM. 5c and 5d analogs caused a potent inhibitory activity on P2X7-induced dye uptake. Dextran Rhodamine exclusion measurements after 24 h of continuous treatment with triazole derivatives indicated a moderated toxicity for all molecules. In conclusion, this study showed that a series of new hybrid 1,2,3-triazolic naphthoquinones reduces P2X7R-induced dye uptake into murine macrophages. In silico analysis indicates a good pharmacokinetic profile and molecular docking results of these analogs indicate the potential to bind into an allosteric site located into the P2X7R pore and juxtaposed with the ATP binding pocket. In this manner, the compounds 5c and 5d may be used as a scaffold for new P2X7R inhibitors with reduced toxicity, and good anti-inflammatory activity. [ABSTRACT FROM AUTHOR]

Highlights • Environmental-friendly synthesis of 1-benzyl-4-phenyl-1H-1,2,3-triazole (BPT). • Non-toxic corrosion inhibitor with average best efficiency of 81% at 2.13 mmol L−1. • BPT acts as a mixed inhibitor for mild steel in HCl 1 mol L−1. • New approach to classical electrochemical analyses. • Atomic Force Microscopy shows the formation of protective film. Abstract 1-benzyl-4-phenyl-1H-1,2,3-triazole was prepared using an environmental friendly and facile synthetic procedure and its performance as an organic corrosion inhibitor for mild steel in 1.0 mol L−1 HCl was investigated using four different methods. An average efficiency of 81.7% was obtained with 2.13 mmol L−1 solutions of the organic compound. A new approach to classical electrochemical analyses confirms the inhibitor adsorption on the metal surface. Temperature effect studies in the oxidation inhibition behavior as well as calculated thermodynamic parameters are consistent with a chemisorption process and Atomic Force Microscopy shows the formation of a protective film. [ABSTRACT FROM AUTHOR]

Abstract This work reports a novel and highly efficient methodology for the synthesis of Schiff bases of 4-amino-1,2,4-triazole derivatives (3a-h) by the condensation of 4-amino-5-methyl-3-oxo-2-tosyl-1,2,4-triazol-3-one (2) derivative with various aromatic aldehydes under ultrasound irradiation. The major advantages of the reported method are its operational simplicity, extremely mild reaction conditions, short reaction times, and excellent yields. The structures of the synthesized compounds were elucidated by IR, 1H NMR, 13C NMR, elemental analysis, and the X-ray crystallography (for compound 3f). The antioxidant activity of the synthesized compounds was determined by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method. The IC 50 value of synthesized Schiff bases were calculated and compared with standard BHA. All compounds showed excellent activity with inhibition values in the range of 71.22 ± 0.98–96.42 ± 0.02% at 1.20 μM. The newly synthesized compounds were also evaluated for angiotensin I-converting enzyme (ACE) inhibition. The results were compared to captopril as a reference drug. All compounds showed ACE inhibition activity from 66% to 95%. Moreover, the synthetic compounds displayed virtually no cytotoxicity. The docking of chemical compounds in the ACE active site revealed possible inhibitory effect of all compounds on the catalytic activity of the enzyme, which would satisfactorily explain the anti-hypertensive effect of these compounds. Graphical abstract Image 107 Highlights • A series of Schiff bases of 4-amino-1,2,4-triazole derivatives under ultrasound irradiation were synthesized. • Ultrasound irradiation method was more efficient than conventional thermal heating. • All the synthesized compounds (3a–h) exhibited antioxidant properties. • The Schiff bases have shown significant inhibitory action against ACE. • The molecular modelling of the tested compounds to angiotensin I-converting enzyme was investigated. [ABSTRACT FROM AUTHOR]

Abstract Malaria, caused by protozoan parasites of the genus Plasmodium especially by the most prevalent parasite Plasmodium falciparum , represents one of the most devastating and common infectious disease globally. Nearly half of the world population is under the risk of being infected, and more than 200 million new clinical cases with around half a million deaths occur annually. Drug therapy is the mainstay of antimalarial therapy, yet current drugs are threatened by the development of resistance, so it's imperative to develop new antimalarials with great potency against both drug-susceptible and drug-resistant malaria. Triazoles, bearing a five-membered heterocyclic ring with three nitrogen atoms, exhibit promising in vitro antiplasmodial and in vivo antimalarial activities. Moreover, several triazole-based drugs have already used in clinics for the treatment of various diseases, demonstrating the excellent pharmaceutical profiles. Therefore, triazole derivatives have the potential for clinical deployment in the control and eradication of malaria. This review covers the recent advances of triazole derivatives especially triazole hybrids as potential antimalarials. The structure-activity relationship is also discussed to provide an insight for rational designs of more efficient antimalarial candidates. Graphical abstract Triazoles represents a fruitful matrix for the development of various new drugs, and some derivatives exhibited promising in vitro antiplasmodial and in vivo antimalarial activities. This review covers the recent advances on triazole derivatives as potential antimalarials. The structure-activity relationship is also discussed for further rational designs of more active triazole derivatives. Image 1 Highlights • Triazole derivatives possess promising in vitro antiplasmodial and in vivo antimalarial properties. • This review covers the recent advances of new triazole derivatives as potential antimalarials. • The structure-activity relationship is also discussed. [ABSTRACT FROM AUTHOR]

In this work, we prepared 3-(p-methyl) phenyl-5-thionyl-1,2,4-triazoline (C1). The nanostructure of the prepared C1 compound was fabricated by assembling on silver nanoparticles (AgNPs). The ultraviolet and transmission electron microscope analyses confirm the assembling of the C1 compound on AgNPs. The effects of the C1 compound on the removal of iron (II) from iron-contaminated samples (prepared in the laboratory) and industrial wastewater samples (produced water from oil processing facility) were studied before and after their assembling on AgNPs. The removal of iron was studied at different concentrations of FeSO4 solution (5, 14, and 39 mg/L), and field sample concentration was 661 mg/L. In addition, the removal of iron (II) was investigated at different times. The prepared compound shows high efficiency in removing the iron ions from the used water samples. The AgNPs have a good role in enhancing the removal of iron ions from the water samples. Quantum chemical descriptors using density function theory with the nonlocal correlation functional B3LYP with 6-311G ++ (p,d) basis set implemented in Gaussian 09 program were EHOMO and ELUMO. The output of the study pronounces that the C1 molecule can act as a chelating agent for iron (II). [ABSTRACT FROM AUTHOR]

Abstract Unsymmetrical dimethylhydrazine (UDMH) is a rocket propellant for carrier rockets and missiles. UDMH is environmentally hostile compound, which easily forms a variety of toxic products of oxidative transformation. The liquidation of unused UDMH from retired launch sites is performed by the complete burning of UDMH-containing wastes. Due cyclicity of the burning equipment the UDMH-containing wastes are subject of prolonged storage in contact with atmospheric oxygen and thus contains a complicated mixture of UDMH degradation products. High performance liquid chromatography (HPLC), high resolution mass spectrometry (HRMS) and NMR were used for the isolation on characterization of new highly polar and potentially toxic UDMH transformation products in the mixture. Two series of unreported isomers with high ionization cross section in electrospray ionization were isolated by repeated preparative HPLC. The structures of the isomers were established by tandem HRMS and NMR. The cytotoxicity of the isolated compounds has been preliminarily studied and found to be similar to UDMH or higher. Graphical abstract Image 1 Highlights • A waste product containing UDMH and it's derivatives was studied. • Five UDMH degradation products were isolated by means of preparative HPLC. • The structure was confirmed by NMR and tandem mass-spectrometry. • The cytotoxicity has been preliminarily studied. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • A novel 1,2,3-triazole derivative of lithocholic acid is prepared. • Geometrical properties are investigated using DFT study. • FMO, charge analysis, TDOS. RDG, ESP have been investigated. • Non-linear optical properties are studied. • Molecular docking studies as potential PTP 1B enzyme inhibitor. Abstract We have reported synthesis of a novel 1,2,3-triazole conjugate of lithocholic acid by 1,3-dipolar cycloaddition reaction. The molecular properties such as geometry, conformations, bond lengths and dihedral angles were investigated theoretically. The bond order analysis was performed using Wiberg bond order (WBO), Fuzzy bond order (FBO) and Laplacian bond order (MBO) method. Electronic properties of molecule such as electrostatic surface potential analysis, frontier molecular orbital analysis, reduced density gradient, total density of states, and global chemical reactivity indices have been investigated. The nonlinear optical properties were also investigated. Total dipole moment, mean polarizability and hyperpolarizability were found to be much higher than standard urea molecule which suggests that it could act as potential NLO material. The molecular docking calculations are also performed to investigate its potential as PTP 1B enzyme inhibitor. [ABSTRACT FROM AUTHOR]

Abstract Previous research studies confirm that molecules containing 1,2,3-triazole moiety are potential anticancer agents which elevates effectiveness and reduces drug resistance. Present study was aimed to evaluate the anticancer activity of the synthesized novel title compound 2-(1-benzyl-5-methyl-1H-1,2,3-triazol-4-yl)-4-(2-chlorophenyl)-6-methoxypyridine (BTCP). The structural and spectral characteristics of BTCP were studied and compared with DFT results. NBO, HOMO and LUMO energies, Mulliken atomic charges and molecular electrostatic potential surface were investigated. The bioavailability of BTCP was confirmed by pharmacological investigations using Molinspiration and PreADMET online servers. Molecular docking studies verified the inhibitory nature of BTCP against human topoisomerase IIα enzyme (1ZXM) over standard drug doxorubicin. MTT assay technique has been employed to study anticancer activity of BTCP with three human cancer cell lines (A549, MDAMB-231, PC-3) along with existing drug doxorubicin. The results of docking and anticancer activity specify that BTCP could be regarded as an alternative anticancer drug. Graphical abstract Image 1 Highlights • SCXRD and spectral characteristics of novel BTCP were studied. • NBO, MPA, NPA, HOMO-LUMO and MEP of BTCP were described. • Molecular docking studies were performed. • Anticancer activity using MTT assay were investigated. [ABSTRACT FROM AUTHOR]

Abstract A new pyrazolotriazole derivative, namely, 1-acetyl-6-methyl-1H-pyrazolo [3,2-c][1,2,4]triazole (APT) was synthesized. The corrosion inhibition performance of APT on carbon steel in 1 M hydrochloric acid solution was investigated using potentiodynamic polarization (PDP) and electrochemical impedance spectroscopy (EIS) methods. The results showed that the inhibition efficiency of APT increases with concentration and attains its maximum of 93% at 10−3 M. The potentiodynamic polarization study suggests that APT acts as mixed type inhibitor. The EIS studies show that APT produces a covering layer at the metal/electrolyte interface. The adsorption of this compound on steel surfaces followed a Langmuir adsorption isotherm. DFT calculations at the B3LYP level of theory and the analyses of frontier orbitals allow the determination of the active adsorbed sites of APT on the metal surface, and molecular dynamics simulations further illustrate the most reasonable adsorption configuration. Graphical abstract Image 1 Highlights • Synthesis of a new 1-acetyl-6-methyl-1H-pyrazolo [3,2-c][1,2,4]triazole derivative (APT). • 3D structure is elucidate using XRD and confirmed by DFT calculations. • APT corrosion inhibition on carbon steel in 1 M HCl solution is investigated. • The inhibition efficiency of APT increases with concentration. • MD simulations suggest the parallel adsorption model of APT on iron substrate. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Twenty four novel bioactive compounds consist pyrrolopyrimidine-triazole were synthesized. • Compounds 4r and 4q showed excellent activity against Mycobacterium tuberculosis H37Rv. • SAR revealed the effect of different substituents on the triazole ring. Abstract A series of novel 1 H -pyrrolo[2,3- d ]pyrimidine-1,2,3-triazole derivatives have been synthesized in good to excellent yields. Through the copper-catalyzed azide-alkyne cycloaddition via reaction of 7-(prop-2-ynyl)-7 H -pyrrolo[2,3- d ]pyrimidine and aryl, heteroaryl and alkyl azides in the presence of CuSO 4 ·5H 2 O and sodium ascorbate. These compounds were evaluated for their in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv strain. Most of these pyrrolopyrimidine-triazole hybrids exhibited good anti tubercular activity. The antimycobacterial assay results showed that the minimum inhibitory concentration of compounds 4q and 4r were 0.78 µg/mL. The molecular docking results also had shown highest Moldock score for same compounds. These novel compounds exhibited good inhibition activities and further structure-activity studies of the derivatives had shown promising features to use in antitubercular therapy. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • New class of Wnt/β-catenin inhibitors discovered from SAR studies of Niclosamide. • The amide SAR of Niclosamide clarified. • Replacement of Niclosamide's amide with a triazole provides Wnt inhibitors. Abstract Dysregulation of the Wnt signaling pathway is an underlying mechanism in multiple diseases, particularly in cancer. Until recently, identifying agents that target this pathway has been difficult and as a result, no approved drugs exist that specifically target this pathway. We reported previously that the anthelmintic drug Niclosamide inhibits the Wnt/β-catenin signaling pathway and suppresses colorectal cancer cell growth in vitro and in vivo. In an effort to build on this finding, we sought to discover new Wnt/β-catenin inhibitors that expanded the chemotype structural diversity. Here, we asked a specific SAR question unresolved in previous SAR studies of Niclosamide's inhibition of Wnt/β-catenin signaling to identify a new structural class of Wnt/β-catenin signaling inhibitors based on a triazole motif. Similar to Niclosamide, we found that the new triazole derivatives internalized Frizzled-1 GFP receptors, inhibited Wnt/β-catenin signaling in the TOPflash assay and reduced Wnt/β-catenin target gene levels in CRC cells harboring mutations in the Wnt pathway. Moreover, in pilot SAR studies, we found the Wnt/β-catenin SAR trends in the anilide region were generally similar between the two chemical classes of inhibitors. Overall, these studies demonstrate the ability to use the SAR of the Niclosamide salicylanilide chemical class to expand the structural diversity of Wnt/β-catenin inhibitors. [ABSTRACT FROM AUTHOR]