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Coffee leaf rust (CLR), caused by Hemileia vastatrix, poses a significant threat to global coffee production, resulting in substantial economic losses. This study explores the effectiveness of triazole derivatives synthesized from glycerol in controlling CLR in conilon coffee (Coffea canephora). In vitro assays evaluated the inhibitory effect of triazole derivatives (4a–4q) at concentrations of 10, 25, 50, 75 and 100 ppm on H. vastatrix urediniospore germination, followed by greenhouse experiments to assess their preventive and curative potential. Preventive and curative sprayings of the four most efficient triazoles were conducted on seedlings inoculated with H. vastatrix at concentrations ranging from 0 to 400 ppm, evaluating severity, sporulation, incubation and latent periods. Triazole derivatives 4b, 4d, 4f and 4o effectively suppressed H. vastatrix urediniospore germination, achieving reductions between 9.9% and 78.8%. In greenhouse trials, these compounds demonstrated preventive efficacy by prolonging incubation and latent periods, reducing sporulation and mitigating rust severity, with triazole 4f exhibiting the highest efficiency. Furthermore, the derivatives showed effectiveness in curative treatments, particularly triazole 4f. Physiological analyses indicated no significant alterations in coffee plant metabolism, suggesting the safety of these compounds for agricultural use. Molecular docking studies elucidated their mechanism of action, suggesting their potential as antifungal agents by interacting with the HvCYP51 enzyme involved in ergosterol biosynthesis. Overall, the study underscores the promising efficacy of glycerol‐derived triazole derivatives in managing CLR, providing sustainable solutions for disease control in agriculture. [ABSTRACT FROM AUTHOR]

AbstractA new cobalt(II) complex, [Co(L)4Cl2]·2C9H10N4O2S (1), was prepared by reaction of CoCl2·6H2O with a sulfonamide, 5-amino-1-tosyl-1H-1,2,4-triazole (L), in double-distilled water and ethanol (1:1 v/v). The sulfonamide was characterized by elemental analysis, and infrared and 1H-NMR spectroscopy, while the Co(II) complex was characterized by elemental analysis, infrared spectroscopy, and single-crystal X-ray diffraction analysis. The X-ray structure analysis reveals that 1 consists of a mononuclear cobalt(II) complex, [Co(L)4Cl2], and two molecules of the co-crystallized ligand (5-amino-1-tosyl-1H-1,2,4-triazole). The cobalt(II) in 1 is coordinated by four triazole ligands and two chlorides in an octahedral environment. The antimicrobial activity and molecular docking of ligand and 1 were investigated. Antibacterial and antifungal activity studies of L and 1 show that both have moderate-to-significant activity against Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus and Bacillus subtilis) bacteria and fungi (Aspergillus niger and Candida albicans). According to molecular docking results, 1 could be a promising compound for developing antibacterial drugs. The docking results provide detailed evidence for the interactions of 1 with dihydropteroate synthase protein (DHPS). The microbial evaluation and molecular docking simulation results may lead to development of new drug candidates against bacterial and fungal strains. [ABSTRACT FROM AUTHOR]

In this paper, triazole derivatives were prepared by a three-step mild reaction using carbon disulfide as starting material. In face of microbial threats, we found that compound 3-cyclopropyl-[1,2,4]triazolo [3,4-b][1,3,4]thiadiazole-6-thiol (C2) has good antibacterial activity, inhibition and clearance ability against biofilms, low hemolytic activity and toxicity, good anti-inflammatory activity. At the same time, we found that B and C series compounds have good metal ion scavenging ability, with removal rates of C series ranging from 47% to 67% and B series ranging from 67% to 87%. [ABSTRACT FROM AUTHOR]

The study aimed to design a novel nanocatalyst, 1,3-Benzothiazole-2,5-diamine supported on nanocellulose (BTDA@CNC), which was characterized using various analytical techniques such as FT-IR, XRD, TGA, SEM, TEM, and CHN. The nanocatalyst was utilized for the synthesis of 1,2,4-triazole derivatives through a simple and efficient three-component reaction between aldehyde derivatives, semicarbazide, and ethanol. The protocol offered advantages such as a simple procedure, high yields, short reaction time, and an environmentally benign method. The nanocatalyst could be readily separated by filter and reused without significant loss of its catalytic efficiency. The synthesized compounds showed moderate activity against both Gram-positive and Gram-negative bacteria, and the antifungal properties of the candida albicans synthesized derivatives were also investigated. [ABSTRACT FROM AUTHOR]

A case of spontaneous chirality generation was observed during a synthetic project studying the allylboration of 1,2,3-triazolic aldehydes. Here, we present computational studies supported by experimental findings targeting the elucidation of border conditions required for the observation of spontaneous chirality generation in the reaction of 1-Ar-1H-1,2,3-triazole-4-carbaldehydes 1a,b with triallylborane. Three possible sources of symmetry breaking were found computationally. Thus, dimerization of the initial reaction products, alcoholates 4a,b, gives dimers 5a,b (homochiral) and 6a,b (heterochiral). The latter were computed to be more stable thermodynamically, which can lead to amplification of the initial stochastic imbalance of the enantiomers of 4a,b via the reservoir mechanism. Furthermore, enantiomeric excess can be increased during the transfer of the second allylic group in the reaction of optically active boronates 4a,b with 1a,b, which was computed to be enantioselective due to the strong activating and stereoregulating properties of the 1,2,3-triazole group. In addition, reactions of borinic esters 8a,b, products of the previous reaction with triallylborane, recovered in each case two molecules of 4a,b of the same handedness, which can lead to additional chirality amplification. Experimentally, reactions of optically active alcohols (+)-R-2a,b with triallylborane provided chiral alcoholates 4a,b, which were reacted with equivalent amounts of corresponding aldehydes 1a,b. Unexpectedly, in two series of 10 experiments each, preferential formation of both enantiomers of the newly formed product was observed: seven times S and three times R in the case of 1a and six times S and four times R in the case of 1b. [ABSTRACT FROM AUTHOR]

The corrosion behavior of steels of various grades in sulfuric acid solutions with the addition of nitrogen-containing corrosion inhibitors has been studied. Compounds containing the 1,2,4-triazole moiety effectively protect low-carbon (St3, St20, 08PS), high-strength (70S2KhA), and stainless steels (1Kh18N9T) not only from corrosion but also from the hydrogen penetration into the metals in concentrated sulfuric acid solutions. In some cases, the degree of steel protection from corrosion by these compounds exceeded 99%. The possibility of creating mixed inhibitors for steel protection containing triazole derivatives and KI has been shown. The rate constants for the main steps of cathodic evolution and hydrogen penetration into steel in sulfuric acid solutions have been determined, and the subsurface concentrations of hydrogen in the metals have been calculated. Triazole derivatives were found to act as inhibitors of hydrogen absorption by steel in H2SO4 solution. The degree of protection of steel from hydrogen absorption can reach 97%. It has been shown that triazole derivatives act as complex inhibitors of steel corrosion in sulfuric acid solutions because, along with strong inhibition of metal corrosion, they prevent hydrogen absorption by steel. [ABSTRACT FROM AUTHOR]

Objective: Encouraged by the significant anticancer activities of benzimidazole, piperazine, and 1,2,3-triazole containing derivatives and based on the need for the development of new EGFR targeting antibreast cancer agents, our group now interested to synthesize new benzimidazole-piperazine-1,2,3-triazoles (VIIa–VIIn) as in vitro antibreast cancer and anti-EGFR agents. Methods: In this study, we focused on the synthesis of benzimidazole-piperazine-1,2,3-triazoles. As well, the in vitro antibreast cancer activity of compounds (VIIa–VIIn) against MDA-MB-231 and MCF-7 cell lines, and anti-EGFR activity of few compounds were studied via IC50 values. Results and Discussion: Compounds (1-methyl-1H-benzo[d]imidazol-2-yl)(4-((1-(p-tolyl)-1H-1,2,3-triazol-4-yl)methyl)piperazin-1-yl)methanone (VIIb), (4-((1-(4-fluorophenyl)-1H-1,2,3-triazol-4-yl)methyl)piperazin-1-yl)(1-methyl-1H-benzo[d]imidazol-2-yl)metha none (VIIe), (4-((1-(3,5-dichlorophenyl)-1H-1,2,3-triazol-4-yl)methyl)piperazin-1-yl)(1-methyl-1H-benzo[d]imidazol-2-yl)methanone (VIIh), and (4-((1-(4-chloro-3,5-dimethoxyphenyl)-1H-1,2,3-triazol-4-yl)methyl)piperazin-1-yl)(1-methyl-1H-benzo[d]imidazol-2-yl)methanone (VIIl) displayed higher activity against two cell lines than the Erlotinib. Furthermore, compounds (VIIb), (VIIe), and (VIIh) displayed greater inhibition against tyrosine kinase EGFR than the Erlotinib. The results of molecular docking studies of (VIIb), (VIIe), (VIIh), and (VIIl) as EGFR (PDB ID: 4HJO) targeting agents were found to be supportive with corresponding IC50 data. Conclusions: We propose that mechanism of in vitro antibreast cancer activity of the investigated compounds, possibly will due to the tyrosine kinase EGFR inhibition. [ABSTRACT FROM AUTHOR]

The quest for and development of combinational chemotherapeutic medicines with various modes of action and low side effects is an essential element of cancer treatment. Aside from developing wholly novel drugs with chemical properties that are obviously distinct from current ones, another strategy involves combining two or more pharmacophores into a sinSgle molecule. The method for making several 1,2,4-triazole derivatives is detailed in the scheme. By 5-Mercapto-3-pyrimidinyl-1,2,4 triazole with various substituted benzyl halides, a total of 7 distinct 1,2,4-triazole derivatives were obtained. Combustion Analysis, TLC, IR, MS and other methods were used to confirm the physical and analytical properties of the newly synthesized 1,2,4-triazole derivatives. Compounds TP1-TP7 exhibit IC50 values ranging from 41.12 M to 61.11 M, with compound TP6 having the greatest activity against the murine melanoma (B16F10) cell line. TP6 was discovered to have more strong anticancer action in anti-cancer screening. As a result, we believe that the findings of this study may pave the way for the creation of anticancer drugs with high efficacy and fewer side effects. As a result, 1,2,4-triazol-3-pyrimidine-based compounds may have a broad anticancer range and serve as a potential lead molecule in different malignancies. [ABSTRACT FROM AUTHOR]

This study evaluated 14 new 4,5,6,7‐tetrabromo‐1H‐benzo[d][1,2,3]triazole derivatives (3a‐n) for their antimicrobial activities, identifying compound 3k as the most effective. In vivo oral toxicity tests confirmed its non‐toxic nature. Predictive ADME analysis indicated favorable drug development properties. Molecular docking and dynamics studies were performed to investigate the interactions of compound 3k with Mycobacterium TB (PDB ID 2X22) and glucosamine‐6‐phosphate synthase (PDB ID 2VF5). The reactivity properties and reactive sites were determined using DFT‐derived HOMO and LUMO orbitals, along with MEP, and ESP maps, providing insights into the electron density, electrophilicity, and nucleophilicity. The electronic properties of the TD‐DFT and IEFPCM models were analyzed in solvents such as acetonitrile, ethanol, and DMSO and results were compared using UV‐Vis spectroscopy. Structural–activity relationship (SAR) investigations elucidated biological activities. [ABSTRACT FROM AUTHOR]

Background: The increasing prevalence of diabetes and the side effects associated with current medications necessitate the development of novel candidate drugs targeting alpha-glucosidase as a potential treatment option. Methods: This study employed computer-aided drug design techniques to identify potential alpha-glucosidase inhibitors from the PubChem database. Molecular docking was used to evaluate 81,197 compounds, narrowing the set for further analysis and providing insights into ligand-target interactions. An ADMET study assessed the pharmacokinetic properties of these compounds, including absorption, distribution, metabolism, excretion, and toxicity. Molecular dynamics simulations validated the docking results. Results: 9 compounds were identified as potential candidate drugs based on their ability to form stable complexes with alpha-glucosidase and their favorable pharmacokinetic profiles, three of these compounds were subjected to the molecular dynamics, which showed stability throughout the entire 100 ns simulation. Conclusion: These findings suggest promising new alpha-glucosidase inhibitors for diabetes treatment. Further validation through in vitro and in vivo studies is recommended to confirm their efficacy and safety. [ABSTRACT FROM AUTHOR]

Prostate cancer is a well-known disease that has gained significant attention in recent years. To improve and suggest new compounds with anticancer activity, it has become essential to identify new proposed agents through innovative and reliable methods such as computational small molecule discovery methods. In this regard, 3D-QSAR and Molecular Docking studies have been conducted on disubstituted 1,2,3-triazole derivatives as antiproliferative analogs, using static methods to find the right model. The study established 3D-QSAR model based on Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Index Analysis (CoMSIA). The best model was obtained with CoMFA model (Q2 = 0.696, R2 = 0.992, R = 0.985) and CoMSIA model (Q2 = 0.582, R2 = 0.992, R = 0.984) statistical coefficients. To determine the predictive power of the model, we need to calculate the parameters of k, Roy, Golbraikh, and Tropsha for the test set and the y, SEE, and t-F randomization tests for the training set. Docking's results suggest that amino acids (PDB; 3 ERT), Asp351, Leu384, Arg394, Phe404, Leu346, Leu525, and Thr347, have a significant interest in anticancer activity. The CoMFA model's steric and electrostatic field contours were studied to determine the results further. The study suggests four new antiproliferative agents that have demonstrated reliability through ADMET and toxicophore methods. [ABSTRACT FROM AUTHOR]

The reaction of thiophene-2-carbohydrazide 1 or 5-bromothiophene-2-carbohydrazide 2 with various haloaryl isothiocyanates and subsequent cyclization by heating in aqueous sodium hydroxide yielded the corresponding 4-haloaryl-5-(thiophen-2-yl or 5-bromothiophen-2-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione 5a-e. The triazole derivatives 5a and 5b were reacted with different secondary amines and formaldehyde solution to yield the corresponding 2-aminomethyl-4-haloaryl-2,4-dihydro-3H-1,2,4-triazole-3-thiones 6a–e, 7a–e, 8, 9, 10a and 10b in good yields. The in vitro antimicrobial activity of compounds 5a–e, 6a–e, 7a–d, 8, 9, 10a and 10b was evaluated against a panel of standard pathogenic bacterial and fungal strains. Compounds 5a, 5b, 5e, 5f, 6a–e, 7a–d, 8, 9, 10a and 10b showed marked activity, particularly against the tested Gram-positive bacteria and the Gram-negative bacteria Escherichia coli, and all the tested compounds were almost inactive against all the tested fungal strains. In addition, compounds 5e, 6a–e, 7a–d and 10a exhibited potent anti-proliferative activity, particularly against HepG-2 and MCF-7 cancer cell lines (IC50 < 25 μM). A detailed structural insight study based on the single crystals of compounds 5a, 5b, 6a, 6d and 10a is also reported. Molecular docking studies of the highly active antibacterial compounds 5e, 6b, 6d, 7a and 7d showed a high affinity for DNA gyrase. Meanwhile, the potent anti-proliferative activity of compounds 6d, 6e and 7d may be attributed to their high affinity for cyclin-dependent kinase 2 (CDK2). [ABSTRACT FROM AUTHOR]

Cruzipain (CZP), the major cysteine protease present in T. cruzi, the ethiological agent of Chagas disease, has attracted particular attention as a therapeutic target for the development of targeted covalent inhibitors (TCI). The vast chemical space associated with the enormous molecular diversity feasible to explore by means of modern synthetic approaches allows the design of CZP inhibitors capable of exhibiting not only an efficient enzyme inhibition but also an adequate translation to anti-T. cruzi activity. In this work, a computer-aided design strategy was developed to combinatorially construct and screen large libraries of 1,4-disubstituted 1,2,3-triazole analogues, further identifying a selected set of candidates for advancement towards synthetic and biological activity evaluation stages. In this way, a virtual molecular library comprising more than 75 thousand diverse and synthetically feasible analogues was studied by means of molecular docking and molecular dynamic simulations in the search of potential TCI of CZP, guiding the synthetic efforts towards a subset of 48 candidates. These were synthesized by applying a Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) centered synthetic scheme, resulting in moderate to good yields and leading to the identification of 12 hits selectively inhibiting CZP activity with IC50 in the low micromolar range. Furthermore, four triazole derivatives showed good anti-T. cruzi inhibition when studied at 50 μ M; and Ald-6 excelled for its high antitrypanocidal activity and low cytotoxicity, exhibiting complete in vitro biological activity translation from CZP to T. cruzi. Overall, not only Ald-6 merits further advancement to preclinical in vivo studies, but these findings also shed light on a valuable chemical space where molecular diversity might be explored in the search for efficient triazole-based antichagasic agents. [ABSTRACT FROM AUTHOR]

A series of 5-methyl-1,2,4-triazol-3-ones containing salicyl or isatin moieties were synthesized by using conventional and microwave heating techniques. In microwave heating, the compounds were synthesized by using both a monomod microwave reactor and domestic type microwave oven and their results were compared. The synthesized compounds were evaluated for their urease inhibitory activities. Among the synthesized compounds two isatin containing 1,2,4-triazol-3-one derivatives (IC50 = 0.5230±0.0318 and 0.4860±0.0317 µM) showed higher activities than salicyl containing derivatives (IC50 = 0.5451±0.0315 and 0.7181±0.0345 µM), while standard thiourea showed IC50= 0.5027±0.0293 µM activity. [ABSTRACT FROM AUTHOR]

In this methodology, a nanomagnetic copper catalyst prepared via the immobilization of CuCl2 on the surface of Fe3O4@SiO2-APA-Amide/Imid ligand and its structure identified by several spectroscopic techniques including XRD, FT-IR, VSM, SEM, TEM, ICP-OES, TGA, EDX and elemental mapping analysis. This Fe3O4@SiO2-APA-Amide/Imid-CuCl2 nanomaterial can catalyze the preparation of 1,2,3-triazole derivatives through reactions of alkyne derivatives with NaN3 and aryl halides under ecofriendly conditions. It is noteworthy that the 1,2,3-triazole products were obtained with high yields when 2-phenylthiirane was used instead of aryl halides. In this research, one-pot three-component reactions were successfully performed in water, and the corresponding triazole products were obtained with high to excellent yields. After the end of the reaction, the Fe3O4@SiO2-APA-Amide/Imid-CuCl2 catalyst was recovered by magnetic separation and reused for 8 runs with a constant efficiency. [ABSTRACT FROM AUTHOR]

Objective: A series of 4-amino-5-((2,4-substituted phenoxy)methyl)-4H-1,2,4-triazole-3-thiol derivatives (Ia–Ib) were synthesized and tested as aromatase enzyme inhibitor. Methods: 4-Amino-5-((2,4-substituted phenoxy)methyl)-4H-1,2,4-triazole-3-thiol derivatives (Ia–Ib) were synthesized via fusion of substituted phenoxycarboxylic acid derivatives with thiocarbohydrazide. Three series of the newly title compounds were prepared by reaction of (Ia–Ib) with aromatic acid derivatives in presence of POCl3 to give [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives (IIa–IIh) or by reaction with phenacyl bromide derivatives in presence of sodium acetate to produce [1,2,4]triazolo[3,4-b][1,3,4]thiadiazine derivatives (IIIa–IIIh). Moreover, (Ia–Ib) were used as a precursor for synthesizing of [1,2,4]triazolo[3,4-b][1,3,4]thiadiazine derivatives (Va–Vd) by reaction with dibromochalcone compounds (IVa–IVb) in presence of triethylamine. The aromatase activities of the newly created compounds were examined. Results and Discussion: Seven triazoles were shown to have significant aromatase inhibitory activity (IC50 = 0.07–1.92 µM). It's interesting to note that analogue (Vb), which substituted a p-chlorophenyl ring at the triazole ring, had the greatest aromatase-inhibitory action (IC50 = 70 µM). Conclusions: The result of the present work indicated that compound (Vb) would be valuable as a potent anticancer agent. Moreover, docking study has been done into aromatase cytochrome P450 enzyme active site (PDB ID: 3EQM) for lead optimization of the aforementioned compounds as prospective tyrosine kinase inhibitors. [ABSTRACT FROM AUTHOR]

Objective: Coumarin and triazole moiety itself is well known to have wide range of biological properties including antibacterial activities. In this work, we have designed and synthesized a series of novel coumarin based 1,2,3-triazole derivatives (VIa–VIi) and reported them as potent antibacterial agent. Methods: All the synthesized compounds were characterized using different spectroscopic methods. The antibacterial properties of our designed compounds were evaluated by calculating the minimum inhibitory concentration (MIC) against the bacterial panel Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa), Staphylococcus aureus (S. aureus), and Bacillus subtilis (B. subtilis). Further, molecular docking analysis were also performed in order to determine the binding modes and binding energies of the potent hybrids. The in silico method has been used for determining the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of (VIc), (VId), (VIg), and (VIh). Results and Discussion: Here, we have successfully synthesized nine novel coumarin based 1,2,3-triazole conjugates using cycloaddition reaction. All the compounds were found to be active against the tested bacterial panel with MIC values ranging from 12.5 to 200 µg/mL. Among them four compounds (VIc), (VId), (VIg), and (VIh) showed broad spectrum of antibacterial activities. Out of these four, the compound (VIh) showed excellent inhibitory action against B. subtilis and compounds (VIg), (VIh) showed great inhibition activity against S. aureus in comparison to the standard drug streptomycin. The molecular docking study also revealed the binding capabilities of our designed compounds with the different active site of the protein (PDB ID: 4OZ5) extracted from B. subtilis with great affinity. Conclusions: From the calculated MIC values, we can conclude that our compounds can act as a potent antibacterial agent against the tested bacteria panel. The in silico results also help to understand the mode of inhibitory action and justify the potential of the synthesized compounds as excellent antibacterial agent. [ABSTRACT FROM AUTHOR]

According to Article 12 of Regulation (EC) No 396/2005, EFSA has reviewed the maximum residue levels (MRLs) currently established at European level for the pesticide active substance difenoconazole. To assess the occurrence of difenoconazole residues in plants, processed commodities, rotational crops and livestock, EFSA considered the conclusions derived in the framework of Council Directive 91/414/EEC, the MRLs established by the Codex Alimentarius Commission as well as the European authorisations reported by Member States and the UK (including the supporting residues data). Based on the assessment of the available data, MRL proposals were derived, and a consumer risk assessment was carried out. Some information required by the regulatory framework was missing and a possible acute risk to consumers was identified. Hence, the consumer risk assessment is considered indicative only, some MRL proposals derived by EFSA still require further consideration by risk managers and measures for reduction of the consumer exposure should also be considered. [ABSTRACT FROM AUTHOR]

Many 1,2,4-triazole derivatives have high biological activity. They are of interest for scientific and practical human activity as potential drugs and pesticides. In this work, we report a synthesis of a series of new 3-amino-1,2,4-triazole derivatives containing an alkylamide moiety. It was found that the amidoalkylation of 3-amino-1,2,4-triazole N-(1,2,2,2-tetrachloroethyl)carboxamides in the presence of triethylamine occurred selectively at the endocyclic nitrogen atom N-1 with the formation of the corresponding N-(1-(5-amino-1H-1,2,4-triazol-1-yl)-2,2,2-trichloroethyl)carboxamides. The reaction products were isolated in 79–85% yields and characterized by 1H NMR and 13C NMR spectroscopy. To unambiguously establish the structure of the obtained compounds, we carried out X-ray diffraction analysis for N-(1-(5-amino-1H-1,2,4-triazol-1-yl)-2,2,2-trichloroethyl)-3-methylbutanamide. [ABSTRACT FROM AUTHOR]

BACKGROUND: To further develop potential natural fungicides, two series of new acrylopimaric acid triazole derivatives were synthesized, and their antifungal activities were tested and evaluated. RESULTS: In vitro antifungal activity results indicated that compound 5m exhibited significant inhibitory activity against Rhizoctonia solani with an half maximal effective concentration (EC50) value of 1.528 mg/L. Its antifungal effect was comparable to that of the commercially available fungicide fluconazole, epoxiconazole and propiconazole (EC50 values of 1.441, 0.815 and 1.173 mg/L). Subsequently, in vivo studies were conducted on compound 5m, which revealed its significant protective and curative effects against R. solani. In addition, physiological and biochemical studies showed that compound 5m could disrupt the morphology and ultrastructure of R. solani mycelium, increase cell membrane permeability, inhibit ergosterol synthesis, and enhance the activity of defense enzymes in rice plants. Three‐dimensional quantitative structure–activity relationship (3D‐QSAR) studies revealed that the molecular structure significantly influenced the binding of compound 5m to the receptor, thereby enhancing its antifungal activity. CONCLUSION: Compound 5m exhibits excellent antifungal activity against R. solani, making it a promising candidate fungicide for the prevention and control of R. solani. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

1,2,4-Triazole derivatives are highly versatile nitrogen-rich heterocyclic compounds known for their wide-ranging biological activities, including antimicrobial, antifungal, antiviral, and anticancer properties. This review article explores the synthesis of these derivatives, focusing on their applications as potent antimicrobial agents. Various synthetic methodologies, such as classical cyclization reactions and modern, greener approaches like microwaveassisted and metal-catalyzed methods, are discussed in detail. The structure-activity relationships (SAR) governing antimicrobial efficacy are analyzed, along with the role of substituent modifications in enhancing the activity of 1,2,4-triazoles. Insights into future directions for the development of novel triazole derivatives for combating drug-resistant pathogens are also provided. [ABSTRACT FROM AUTHOR]

The document is a contents list for the journal "Dalton Transactions: An International Journal of Inorganic Chemistry," published by The Royal Society of Chemistry. It includes various articles covering topics such as synthetic approaches and applications of inorganic compounds, electrode materials, metal-organic frameworks, and catalytic investigations. Additionally, the document includes a correction notice for an article titled "Molybdenum-maltolate as a molybdopterin mimic for bioinspired oxidation reaction." The correction notice provides the correct information for the article, including the names of the authors and the correct page numbers. [Extracted from the article]

Incorporating transition metal atoms into metal–molecule–metal junctions presents opportunities for exploring the electronic properties of coordination complexes, organometallics and metal–organic materials on the single molecule level. Recent single molecule conductance studies have shown that in situ incorporation of electrode metal atoms into coordination chains formed in the junction can occur with deprotonated, negatively charged organic ligands, such as the imidazolate (Im−) anion. However, the mechanism and chemical principles, such as the role of the charge state of the ligand, for the construction of such coordination chains are still debated. Here, we probe the role of the ligand charge state and electronic structure in single-molecule conductance and formation of metal–molecule coordination chains. We perform break junction measurements with triazole isomers, which can bridge junctions both in their neutral and charged forms, and find that prior deprotonation of the ligands is not required for coordination complex assembly, but can affect the molecular conductance and junction formation probability. Our results indicate that coordination chains can form with neutral ligands, as long as the electron density in the frontier MOs is concentrated at the binding sites and along the direction of pulling, promoting ligand binding and incorporation of gold atoms into the junction during elongation. Our findings may provide insight into design principles for in situ assembled molecular wires with transition metal atoms and open the door to electronic and spintronic studies of such materials. [ABSTRACT FROM AUTHOR]

An efficient palladium‐catalyzed three‐component reaction for the synthesis of tricyclic fused 1,2,3‐triazole derivatives from amino‐NH‐1,2,3‐triazoles, isocyanide and iodoarenes has been developed, involving three new bonds formation by one manipulation in moderate to good yields with excellent functional group tolerance. Moreover, it is also suitable for other N‐heterocyclic substrates including pyrazole, imidazole, indole, tetrazole and its derivatives. [ABSTRACT FROM AUTHOR]

1,2,4-Triazole derivatives have a wide range of biological activities. The most well-known drug that contains 1,2,4-triazole as part of its structure is the nucleoside analogue ribavirin, an antiviral drug. Finding new nucleosides based on 1,2,4-triazole is a topical task. The aim of this study was to synthesize ribosides and deoxyribosides of 1,2,4-triazole-3-thione derivatives and test their antiviral activity against herpes simplex viruses. Three compounds from a series of synthesized mono- and disubstituted 1,2,4-triazole-3-thione derivatives were found to be substrates for E. coli purine nucleoside phosphorylase. Of six prepared nucleosides, the riboside and deoxyriboside of 3-phenacylthio-1,2,4-triazole were obtained at good yields. The yields of the disubstituted 1,2,4-triazol-3-thiones were low due to the effect of bulky substituents at the C3 and C5 positions on the selectivity of enzymatic glycosylation for one particular nitrogen atom in the triazole ring. The results of cytotoxic and antiviral studies on acyclovir-sensitive wild-type strain HSV-1/L2(TK+) and acyclovir-resistant strain (HSV-1/L2/RACV) in Vero E6 cell culture showed that the incorporation of a thiobutyl substituent into the C5 position of 3-phenyl-1,2,4-triazole results in a significant increase in the cytotoxicity of the base and antiviral activity. The highest antiviral activity was observed in the 3-phenacylthio-1-(β-D-ribofuranosyl)-1,2,4-triazole and 5-butylthio-1-(2-deoxy-β-D-ribofuranosyl)-3-phenyl-1,2,4-triazole nucleosides, with their selectivity indexes being significantly higher than that of ribavirin. It was also found that with the increasing lipophilicity of the nucleosides, the activity and toxicity of the tested compounds increased. [ABSTRACT FROM AUTHOR]

In the presence of ethanol solvent and glacial acetic acids, triazole reacted with different aromatic aldehydes such as 4-methoxybenzaldehyde, 4-hydroxybenzaldehyde, and benzaldehyde to form the imines group known as Schiff bases. Triazole Schiff bases are triazole hydrazone and their derivatives, VA, VB, and VC. The structures of these synthetic triazole hydrazone derivatives were characterized by means of FT-IR and mass spectrometry. The purities and quality of the compounds were evaluated using TLC. It was established, that the active ingredient in the synthesised triazole hydrazone was more effective against the infections than cefuroxime. [ABSTRACT FROM AUTHOR]

Since the beginning of click chemistry, 1,2,3-triazoles has been at the center of modern organic chemistry. This versatile framework has found broad applications in organic synthesis, drug discovery, chemical biology, polymer chemistry, supramolecular chemistry, bioconjugation, fluorescent imaging, and materials sciences. Due to tremendous use of 1,2,3-triazoles in chemistry, synthesis of this moiety from the easily available chemicals is desirable. This review covers different conventional and non-conventional approaches adopted for the synthesis of 1,2,3-triazole derivatives. [ABSTRACT FROM AUTHOR]

In our relentless pursuit of developing innovative antibacterial derivatives, we have successfully generated and evaluated a novel series of 1,2,3-triazole derivatives derived from azo dapsone. The synthesis process commenced with the fusion of the dapsone core with the triazole framework, establishing a solid foundation for our synthetic endeavors. Subsequently, the azo dapsone nucleus underwent functionalization using sodium azide, resulting in the creation of an azide derivative (B). To synthesize the desired end 1,2,3-triazoles, a click reaction was employed, combining the azide compound with triple bond derivatives. The structures of all the synthesized compounds were meticulously characterized through the utilization of advanced techniques such as Nuclear Magnetic Resonance (NMR) and Infrared (IR) spectroscopy. Following the successful synthesis and characterization, our focus shifted to evaluating the in vitro antibacterial activity of these compounds against two significant bacterial strains: the gram-positive bacterium Staphylococcus aureus and the gram-negative bacterium Escherichia coli. Among the compounds synthesized, one compound in particular, designated as (H2), exhibited exceptional potency against Staphylococcus aureus with a minimal inhibitory concentration (MIC) of 25 μg/mL, surpassing the activity of all other prepared compounds. Similarly, compound (H1) displayed remarkable efficacy against Escherichia coli with an MIC of 22 μg/mL, outperforming the other end compounds. These findings demonstrate the tremendous potential of our synthetic approach in generating dapsone derivatives with enhanced antibacterial activity. Our research represents a significant step forward in the development of novel and potent antibacterial agents. [ABSTRACT FROM AUTHOR]

A novel 1,2,4-triazole-5-thiol derivative was designed through a series of reactions. Firstly, Azo derivative 1 was synthesized by a general method with two steps, a diazotization reaction in an acidic medium, and a coupling reaction in basic conditions. Secondly, Azo-carboxylic acid 1 reacted with SOCl2 to produce acid chloride derivative 2. Then carbothiamide derivative 3 was synthesized through substitution reaction by reacting 2 with 4-phenyl thiosemicarbazide in pyridine. In the next step, carbothiamide 3 was reacted with sodium hydroxide solution to afford target triazole derivative 4. The structures of all synthesized derivatives were confirmed by techniques (¹H, 13C NMR, IR). Moreover, the triazole derivative 4 was evaluated for its biological activity as an anticancer, antioxidant, and antibacterial. The results presented that compound 4 has moderate antibacterial activity and a high free radical scavenging effect (IC50 30.2 μg/mL) compared to vitamin C (IC50 21 μg/mL). The anticancer activity results presented that compound 4 has a toxic effect on a colon cancer cell line CaCo-2. The potential effect of compound 4 on the 5lqf protein was examined in silico studies. [ABSTRACT FROM AUTHOR]

Purpose: To report a case of endogenous endophthalmitis caused by the dematiaceous fungus Cladophialophora devriesii. Methods: Observational case report and literature review. Case presentation: A 73-year-old female with a history of chronic obstructive pulmonary disease presented with a red and painful left eye. Examination revealed anterior segment inflammation and vitritis, indicative of endophthalmitis. She underwent core vitrectomy and intravitreal injection of vancomycin and amphotericin B. The vitreous sample showed inflammatory cells and fungal hyphae, and systemic amphotericin B and itraconazole were commenced for fungal endophthalmitis. Targeted amplification of the sample for bacterial DNA (V2-V3 region of 16 S rDNA) was negative, but fungal DNA targets (ITS1 and ITS2) were present, and their sequences were consistent with Cladophialophora devriesii. Phenotypic characterisation and sequencing of ITS1 and ITS2, carried out on cultured fungus from the sample, also revealed Cladophialophora devriesii. She received repeated intravitreal injections of voriconazole, and based on the antifungal susceptibility results, her systemic medication was changed to posaconazole. After 12 months, the eye showed no signs of inflammation, and posaconazole therapy was discontinued. After 3 months without antifungal medication, the inflammation recurred, and she was restarted on antifungal therapy for an additional 20 months. Another recurrence occurred 3 months after discontinuation of treatment, and a repeat vitreous sample confirmed the presence of Cladophialophora devriesii. She was started on isavuconazole, but developed seclusio pupillae and painful secondary glaucoma. Due to the duration and severity of the infection, the eye was enucleated. Histopathology revealed persistent fungal elements at the ciliary processes and the posterior lens surface. Conclusions: This second reported case of endogenous endophthalmitis caused by Cladophialophora devriesii illustrates the role of vitreous sampling and molecular methods in diagnosis and treatment of fungal endophthalmitis. Despite early diagnosis and prolonged local and systemic antifungal therapy, it was not possible to achieve long-term control of the fungal infection. [ABSTRACT FROM AUTHOR]

A novel series of pyrrolidinylquinoline–imidazolyl-1,2,3-triazole hybrids were synthesised starting from 2-(pyrrolidine-1-yl)quinoline-3-carbaldehyde. The aldehyde was reacted with o-phenylenediamine to produce benzimidazole derivative which was alkylated with propargyl bromide and then subjected to copper-catalyzed azide–alkyne cycloaddition to afford the desired 1,2,3-triazole derivatives. The cycloaddition step was performed under both traditional stirring and microwave irradiation. All synthesized triazole derivatives were screened for their in vitro antimicrobial activity against various bacterial and fungal pathogens. The majority of the synthesized compounds demonstrated moderate to good inhibition zones compared to the standard drugs. [ABSTRACT FROM AUTHOR]

A series of hybrid compounds with triazole and thiazolidine nuclei connected by a linker has been synthesized and extensively studied. Various synthetic methods for the target compounds have been tested. A microbiological assessment of the obtained compounds was carried out on strains of pathogenic fungi C. albicans, C. non-albicans, multidrug-resistant C. auris, Rhizopus arrhizus, Aspergillus spp. and some dermatophytes and other yeasts. The lowest obtained MIC values for target compounds lie between 0.003 µg/mL and 0.5 µg/mL and therefore the compounds are not inferior or several times better than commercial azole drugs. The length of the acylpiperazine linker has a limited effect on antifungal activity. Some bioisosteric analogues were tested in microbiological analysis, but turned out to be weaker than the leader in activity. The highest activity was demonstrated by a compound with para-chlorobenzylidene substituent in the thiazolidine fragment. Molecular modelling was used to predict binding modes of synthesized molecules and rationalize experimentally observed SAR. The leader compound is twice more effective in inhibiting the formation of germ tubes by Candida albicans yeast cells compared to voriconazole. An increased level of Pdr5, an azoles drug efflux pump was observed, but the increase is lower than that caused by azoles. The results can be useful for further development of more powerful and safe antifungal agents. [ABSTRACT FROM AUTHOR]

Objective: Dehydroepiandrosterone plays an important role in the human beings due to its ability to be converted into androgens and oestrogens. The aim of this paper is to synthesize a series of novel dehydroepiandrosteronyl 1,2,3-triazole derivatives and study the antitumor activity of the synthesized compounds. Methods: Novel dehydroepiandrosteronyl 1,2,3-triazole derivatives were synthesized across the Mitsunobu and click reaction, respectively. The cytotoxicities of the synthesized compounds against HeLa, HGC-27, and HEK-293T cells were determined by MTT assay. Results and Discussion: The results showed that compound (V) (3R,8R,9S,10R,13S,14S)3-(4-(4-methoxyphenyl)-1H-1,2,3-triazol-1-yl)-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro17H-cyclopenta[a]phenanthren-17-one had better inhibitory activity against the tumor cell lines tested. The IC50 value of inhibitory activity on human cervical cancer cell (HeLa) and human gastric cancer cell (HGC-27) was 33.6 and 22.3 μmolL–1, respectively. Conclusions: This work provides useful strategies for the design and synthesis of new steroidal antitumor drugs. The synthesized compounds have certain inhibitory activity on tumor cell growth and proliferation, but have little damage on normal cells, which deserves further study. [ABSTRACT FROM AUTHOR]

Hydrogen‐bonding and halogen‐bonding interactions are important noncovalent interactions that play a significant role in the crystal structure of organic molecules. An in‐depth analysis is given of the crystal packing of two previously reported crystal structures of dihalogenated 1,2,4‐triazole derivatives, namely 3,5‐dichloro‐1H‐1,2,4‐triazole and 3,5‐dibromo‐1H‐1,2,4‐triazole. This work provides insights into the complex interplay of hydrogen‐bonding and halogen‐bonding interactions resulting in the formation of multiple trimeric motifs in the crystal structure of 1,2,4‐triazole derivatives. Analysis of the crystal packing of these isostructural crystal structures revealed that the molecular arrangement in these molecules is primarily stabilized by the formation of different trimeric motifs stabilized by N—H...N hydrogen bonds, N—H...X (X = Cl/Br) halogen bonds and C—X...X halogen‐bonding interactions. Computational studies further revealed that all these trimers are energetically stable. A crystallographic database search further reveals that while the cyclic trimers reported in this study are present in other molecules, structures analyzed in this study are the sole instances where all are present simultaneously. [ABSTRACT FROM AUTHOR]

[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]

Mosquito-repellent textiles are in high demand as a disease-prevention solution for mosquito bites as mosquito-borne diseases proliferate over the world. In, this study selenium nanoparticles (SeNPs) conjugated by synthesized pyridotriazolprymidine derivative VI were utilized to treat 100% cotton, 65/35% cotton/PET, viscose and gauzy cotton fabrics, for mosquito repellency application. The synthesized triazole derivative and the nanoparticles were confirmed by different instrumental techniques. The presence of SeNPs@triazole derivative on the fabrics surface was examined using FT-IR, SEM and EDX. The modified fabrics were tested for repellency to Culex pipiens mosquitoes and the results indicated 100% repellency for 2 h and complete mortality after 1 day, the samples of fabrics are more durable by the ratio of 100% after the 9th washing but decreased for the 10th washing. The cytotoxicity of the treated fabrics showed enhanced compatibility with the human normal fibroblast cell line (BJ1) with no toxic effect. [ABSTRACT FROM AUTHOR]

Modification of marketed drugs is an important way to develop drugs because its safety and clinical applicability. Oxygen-nitrogen heterocycles are a class of important active substances discovered in the process of new drug development. Dolutegravir, an HIV drug with a nitrogen-oxygen heterocycle structure, has the potential ability to inhibit cell survival. In order to find and explore novel anti-tumor drugs, new dolutegravir derivatives bearing different 1,2,3-triazole moieties were prepared via click reactions. In vitro biological experiments performed in several lung cancer cell lines suggested that these novel compounds displayed potent anti-tumor ability. Especially, the compound 9e with a substituent of 2-methyl-3-nitrophenyl and the compound 9p with a substituent of 3-trifluoromethylphenyl were effective against PC-9 cell line with IC50 values of 3.83 and 3.17 µM, respectively. Moreover, compounds 9e and 9p were effective against H460 and A549 cells. Further studies suggested that compounds 9e and 9p could induce cancer cell apoptosis in PC-9 and H460, inhibit cancer cell proliferation, change the cell cycle, and increase the level of reactive oxygen species (ROS) which further induce tumor cell apoptosis. In addition, compounds 9e and 9p increased LC3 protein expression which was the key regulator in autophagy signaling pathway in PC-9 cells. Compound 9e also showed low toxicity against normal cells, and could be regarded as an interesting lead compound for further structure optimization. [ABSTRACT FROM AUTHOR]

A novel triazole derivative was synthesized and characterized by various spectroscopic techniques such as FTIR, NMR and single crystal X-ray diffraction study. The title compound crystallizes in the triclinic space group P 1 ¯ and exhibits inter-molecular hydrogen bonds of the type C–H...O and C–H...N. Hirshfeld surface analysis shows that the major intermolecular interaction is mainly due to H...H contacts. DFT calculations were performed to study their electronic properties. QTAIM and NCI studies were used to investigate the weak interactions in five triazole derivatives including the title compound. [ABSTRACT FROM AUTHOR]

Compounds with a 1,2,4–triazole scaffold serve an essential role in organic synthesis, particularly in the synthesis of bioactive organic compounds; thus, the development of new approaches for modifying this scaffold is a very interesting framework of this study. To contribute to the development of an efficient method for the conversion of anticancer triazoles, a novel series of benzimidazole based 1,2,4‐triazoles was designed and synthesized. All the newly synthesized derivatives were characterized by NMR (1H &13C), FT–IR and mass spectrometry. Among the tested compounds, hybrids 5 b, 5 g exhibited exceptional anticancer susceptibilities with IC50=8.8±0.9, 9.2±1.5 μM against the tested HCA‐7cancer cell line. Anticancer profiles showed that compounds 5 d, 5 i had better anticancer inhibitory potency against a breast cancer cell line MCF‐7with IC50values 8.3±2.1, 10.6±1.2 μM, whereas 5 d, and 5 g showed potent anticancer activity against colorectal cancer cell line HT29 with IC50 values 7.1±±0.9, 7.7±1.2 μM respectively. From docking results, 5 d demonstrated highly stable binding amino acids LeuA : 2247, GlyA : 2449, SerA : 2409, HisA : 2379, AspA : 2373, LysA : 2318, IleA : 2317, IleA : 2246, IleA : 2412, AlaA : 2410, GlnA : 2452, AsnA : 2245, TyrA : 2243, and HisA : 2448, which play a crucial role enabling optimal ligand binding in a crystal structure tyrosine phosphatase mutated in colorectal cancer (PDB: 1WCH). Furthermore, the physicochemical and absorption, distribution, metabolism, and excretion (ADME) filtration molecular properties, estimation of bioactivity, and toxicity scores of these scaffolds were evaluated. [ABSTRACT FROM AUTHOR]

Chalcone and triazole scaffolds have demonstrated a crucial role in the advancement of science and technology. Due to their significance, research has proceeded on the design and development of novel benzooxepine connected to 1,2,3‐triazolyl chalcone structures. The new chalcone derivatives produced by benzooxepine triazole methyl ketone and different aromatic carbonyl compounds. Product structures were established by various spectral techniques such as IR, 1H NMR, 13C NMR, and mass specrometric analysis. Among the tested compounds, two compounds exhibited exceptional antibacterial susceptibilities with MIC (Minimum inhibitory concentration) range of 3.59–10.30 μM against the tested S. aureus strain. Few of the compounds displayed superior antifungal activity against F. oxysporum with MIC value range from 3.25‐4.89 μM, when compared to fluconazole (MIC=3.83 μM). In addition, few derivatives demonstrated equivalent antitubercular action against H37Rv strain with MIC range of 2.16–4.90 μM. The capacity of one of the ligand to form a stable compound on the active site of CYP51 from M. tuberculosis (1EA1) was confirmed by docking studies. Additionally, the chalcone‐1,2,3‐triazole hybrids ADME (absorption, distribution, metabolism, and excretion), molecular characteristics, estimation of toxicity, and bioactivity scores were assessed. [ABSTRACT FROM AUTHOR]

A new approach for synthesizing triazole rings through the application of laccases, copper containing oxidoreductase enzymes is outlined. A series of benzothiazoles and benzimidazoles-functionalized alkynes were initially synthesized utilizing a biocatalysis laccase-based approach. The resultant alkynes were further treated with aryl azides in a 1,3-dipolar cycloaddition reaction facilitated by laccase enzymes to obtain 1,2,3-triazole-fused benzothiazoles and benzimidazoles. [ABSTRACT FROM AUTHOR]

This study focuses on the synthesis of aromatic and heteroaromatic triazole derivatives known for their versatile therapeutic potential in the treatment of cancer, bacterial infections, fungal infections, and malaria. To achieve this, we have developed an efficient synthetic pathway for a wide range of derivatives with a structural motif represented as 2-(4-{[(2-oxo-2H-chromen-4-yl)oxy]methyl}-1H-1,2,3-triazol-1-yl)-N-(4-phenyl-1,3-thiazol-2-yl)acetamide. The structure of the synthesized compounds was determined using 1H and 13C NMR spectroscopy, FT-IR spectroscopy, mass spectrometry, and elemental analysis. Furthermore, this study delves into the antimicrobial and antifungal properties of the coumarin-linked triazole derivatives, highlighting their potential as diverse chemotherapeutic agents with promising clinical applications. Also, the in silico study was performed to assess pharmacokinetics and toxicity profiles. [ABSTRACT FROM AUTHOR]

Objective: Currently, microbial infections are a global threat to human health, and there is an urgent need to develop new and effective antibacterial drugs to treat microbial infections. The main purpose of this article is to study the inhibitory effect of sulfonamide compounds containing 1,2,3-triazole rings on bacteria and fungi, in order to seek new antibacterial drugs. Methods: Several sulfonamide compounds with 1,2,3-triazole rings were prepared and their inhibitory effects on seven common human pathogenic bacteria (E. coli, P. aeruginosa, S. typhimurium, S. aureus, and B. subtili, as s well as the fungi C. albicans, and A. niger) were evaluated. And through MOE and Gaussian software, the new molecular docking simulation and molecular quantification calculation of the synthesized compound were carried out to explain the relationship between the antibacterial effect of the compound and its molecular configuration. Results: The results showed that compounds (VIb), (VId), (VIe), (VIf), (VIi), and (VIj) had good antibacterial activity. Among them, (VIe) and (VIf) had similar inhibitory activity against Candida albicans as the positive control drug fluconazole, and (VI) f also had a certain inhibitory effect on Escherichia coli. Discussion: Through antibacterial experiments, we found that the antibacterial effects of (VIe) and (VIf) were the best among the synthesized compounds. Through molecular docking simulation and molecular quantification calculations, we found that compounds (VIe) and (VI) f had a better docking effect with enzymes and the highest molecular energy. They had higher reaction activity and were easy to interact with microbial enzymes, thus exerting antibacterial effects. At the same time, we found that the introduction of amide bonds containing electron donating groups on the benzene ring in triazole sulfonamide significantly enhances the antibacterial activity of the compound. Therefore, we believe that when the electron cloud density on the 1,2,3-triazole ring increases, the antibacterial effect of the compound will be enhanced. Conclusions: 1,2,3-triazole sulfonamides containing amide bonds can serve as potential antibacterial agents. [ABSTRACT FROM AUTHOR]

Some of triazole derivatives are synthesized by cyclization reaction of thiocarbohydrazide synthesized by reaction of carbon disulphide and aqueous hydrazine; the basic nucleus 3-methyl-4-amino-1,2,4-triazole-5-thione (L) is prepared by reaction of thiocarbohydrazide compound with glacial acetic acid under reflux condition. The compound (L) is subjected to addition reaction with different aldehydes to synthesize Schiff bases 1,3[N,N-Bis(5-methyl-1,3,4- triazole-2-thione)] benzene (L1) and 1,4[N,N-Bis(5-methyl-1,3,4-triazole-2- thione)] benzene (L2). The compounds (L1) and (L2) are confirmed by means of their melting point, FTIR, UV-visible, and ¹H-NMR spectra. [ABSTRACT FROM AUTHOR]

BACKGROUND: Isopropyl 4‐(2‐chloro‐6‐(1H‐1,2,4‐triazol‐1‐yl)benzamido)benzoate (TPB) was a 1,2,4‐triazole benzoyl arylamine derivative with excellent antifungal activity, especially against Gaeumannomyces graminis var. tritici (Ggt). Its mechanism of action was investigated by transmission electron microscopy (TEM) observation, assays of sterol composition, cell membrane permeability, intracellular ATP and mitochondrial membrane potential, and mPTP permeability, ROS measurement, RNA sequencing (RNA‐seq) analysis. RESULTS: TPB interfered with ergosterol synthesis, reducing ergosterol content, increasing toxic intermediates, and finally causing biomembrane disruption such as increasing cell membrane permeability and content leakage, and destruction of organelle membranes such as coarse endoplasmic reticulum and vacuole. Moreover, TPB destroyed the function of adenine nucleotide transferase (ANT), leading to ATP transport obstruction in mitochondria, inhibiting mPTP opening, inducing intracellular ROS accumulation and mitochondrial membrane potential loss, finally resulting in mitochondrial damage including mitochondria swelled, mitochondrial membrane dissolved, and cristae destroyed and reduced. RNA‐seq analyses showed that TPB increased the expression of ERG11, ERG24, ERG6, ERG5, ERG3 and ERG2 genes in ergosterol synthesis pathway, interfered with the expression of genes (NDUFS5, ATPeV0E, NCA2 and Pam17) related to mitochondrial structure, and inhibited the expression of genes (WrbA and GST) related to anti‐oxidative stress. CONCLUSIONS: TPB exhibited excellent antifungal activity against Ggt by inhibiting ergosterol synthesis and destroying ANT function. So, TPB was a novel compound with dual‐target mechanism of action and can be considered a promising novel fungicide for the control of wheat Take‐all. The results provided new guides for the structural design of active compounds and powerful tools for pathogen resistance management. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

An effective approach to 5‐triazolyl‐substituted 6,7‐dihydrobenzo[d]isoxazol‐4(5H)‐ones and 4,5,6,7‐tetrahydrobenzo[d]isoxazoles was developed. The approach included α‐keto bromination of 6,7‐dihydrobenzo[d]isoxazol‐4(5H)‐one followed by nucleophilic substitution of bromine with the azide group. For the preparation of 5‐azido‐6,7‐dihydrobenzo[d]isoxazol‐4(5H)‐one, the carbonyl group at position 4 was reduced to a methylene group under ionic hydrogenation conditions using triethylsilane as a reducing agent. Cu(I)‐catalyzed [2+3] cycloaddition of terminal alkynes to both obtained azides was used for the synthesis of two series of triazolyl derivatives. Compounds, which contain in their structures common for some Hsp90 inhibitors 2,4‐dihydroxy‐5‐isopropylphenyl fragment, were evaluated as antiproliferative agents against two breast cancer cell lines: hormone‐dependent MCF7 and HER2‐positive HCC1954. The lead compound showed half‐maximal inhibitory concentration (IC50) values below 5 μM and induced significant changes in the Hsp90 signaling pathways in HER2‐positive HCC1954 cells. It increased the expression of Hsp70 (used as a pharmacodynamic marker of Hsp90 inhibition) and inhibited the expression of HER2, p‐c‐Met, c‐Met, and p‐AKT. The combination of the selected isoxazole‐triazole hybrid molecule and the earlier described apoptosis inducer LCTA‐3344 demonstrated a significant antiproliferative effect against HCC1954 cells. The lead compound was revealed to be a promising candidate for future anticancer drug design, particularly against aggressive breast cancer positive for HER2. [ABSTRACT FROM AUTHOR]

Three-component reaction between sodium azide, ethyl cyanoacetate or malonitrile and arylglyoxals afforded 4,5-disubstituted 1,2,3-triazole derivatives in high yields. All reactions were conducted in ethanol as an environmentally benign solvent at room temperature without using any catalyst or modifier. Stable solid products were easily isolated and purified by washing with water and diethyl ether. The structures of the compounds were proved by 1H and 13C NMR and IR spectral and elemental analysis data. [ABSTRACT FROM AUTHOR]

This review article examines the synthetic pathways for triazolothiadiazine derivatives, such as triazolo[3,4-b]thiadiazines, triazolo[5,1-b]thiadiazines, and triazolo[4,3-c]thiadiazines, originating from triazole derivatives, thiadiazine derivatives, or thiocarbohydrazide. The triazolothiadiazine derivatives exhibit several biological actions, including antibacterial, anticancer, antiviral, antiproliferative, analgesic, anti-inflammatory, and antioxidant properties. The review article aims to assist researchers in creating new biologically active compounds for designing target-oriented triazolothiadiazine-based medicines to treat multifunctional disorders. [ABSTRACT FROM AUTHOR]