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Oncology research progresses, yet cancer remains the largest medical need. The use of a medication with an accessible lead molecule shows great potential for long-term cancer therapy. It may help target cancer therapy and drug resistance. This work uses FDA-approved, clinically proven compounds to build novel cancer therapeutic ligands to prevent treatment resistance. Based on the reported findings, an in-silico docking experiment was performed using FDA-licensed fungus medication posaconazole. The ALK TK pdb:4cmu ligand and posaconazole docked similarly in the research. Posaconazole’s in silico docking findings were then tested against A549 lung cancer cells. Posaconazole, the lead, underwent an ADME investigation. Given in silico and experimental confirmation, acetyl, benzyl, and benzoyl derivatives of the lead molecule posaconazole was synthesized. IR, mass, 1H NMR, 13C NMR, and elemental analysis were performed on the synthesized compounds. Next, the three variants were evaluated against A549 lung cancer cells. They were then examined by utilizing computational approaches such as molecular docking, DFT analysis, MD simulation, and MMGBSA analysis. The ADME studies were conducted on posaconazole and its derivatives based on the in-vitro cell line investigation. Based on the results of an ADME study, two new ALK TK inhibitors that don’t work as Pgp substrates are good lead candidates. Thus, the present investigation fruitfully reported two lead drug candidates against the issue of resistance in cancer therapy [ABSTRACT FROM AUTHOR]

CB2R are fascinating targets for neuropathic pain and mood disorders because of their improved biological characteristics. Experimental data on 1296 cannabinoid-2 receptor inhibitors with different structural properties were used to develop a QSAR model following OECD guidelines. This study selected the best-predicted model (80:20 splitting ratio) with fitting parameters, such as R2:0.78; F:623.6, Internal validation parameters, such as Q2Loo:0.78; CCCcv: 0.87 and external validation parameters, such as R2ext:0.77; Q2F1:0.7730; Q2F2:0.7730; Q2F3:0.76; CCCext:0.87. Following this, another QSAR model was developed by using a 50:50 split ratio for thetraining and the prediction sets, which were then swapped to evaluate the robustness of the built QSAR model by the 50:50 ratio, which also gives a deeper understanding of the chemical space. In addition, we have confirmed the QSAR result with pharmacophore modelling, and supported by molecular docking, MD simulation, MMGBSA and ADME studies. Thus, this work may enable cannabinoid 2 receptor inhibsitor development. [ABSTRACT FROM AUTHOR]

[Display omitted] Carbazole is a heterocyclic aromatic organic compound that has vast applications in pharmaceuticals, and in biological and material sciences. Carbazole derivatives show various biological activities such as antibiotic, anti-inflammatory, anti-tumor and anti-oxidant activities etc. Synthesis of N -arylated carbazoles has become a major area of interest for scientists due to their applications in organic light-emitting diodes, dye-sensitized solar cells, and other organic electronics. The N -arylated carbazoles have unique properties such as high thermal stability, wide band gap, and excellent electrical and optical properties. The methods used for the N -arylation of carbazoles include transition metal-catalyzed reactions and metal-free reactions. The most common and classical methods for the N -arylation of carbazoles are copper-catalyzed Ullmann coupling reactions, while palladium, nickel, and iron catalysts are also used. This review focuses on all the synthetic methods used for the N -arylation of carbazoles and their applications. [ABSTRACT FROM AUTHOR]

[Display omitted] The combination of heterocycles renders a new possibility to synthesize multicyclic compounds having improved biological activities. Furo[3,2- b ]pyridine is a fused heterocyclic ring system comprising a furan ring attached at the third and second positions of pyridine. These heterocyclic compounds can be easily synthesized from versatile starting materials including pyridine, furan, benzofuran, and benzopyridine via cycloaddition, cycloisomerization, multicomponent, cross-coupling, and Dakin-type reactions by utilizing microwave, copper, and palladium based catalysts. Among the chemical transformations of furo[3,2- b ]pyridine derivatives, the review covered acetylation, addition, condensation, chlorination, Suzuki coupling, Vilsmeier-Haack reaction, and nucleophilic substitution reactions. Furo[3,2- b ]pyridine has attracted remarkable attention from researchers due to its wide range of pharmacological and biological applications as antibiotic, antiviral, antifungal, anticancer, inhibitors of nicotinic acetylcholine receptors, CLKs, e1F4A, DYRKIA, α -glucosidase and β -glucosidase. The purpose of the review is to discuss the chemistry of the title reported during 2019–2024. [ABSTRACT FROM AUTHOR]

Until today, microbial infections epitomize a serious universal health threat. Subsequently, developing a potential antimicrobial prototype remains an urgent, global necessity. Despite several reports discussing the biological utility of some bis-thiazoles, the use of bis-dihydrazothiazoles and their corresponding metal chelates as potent antimicrobials, is yet to be explored. The current report outlines an attempt to fill that void by representing a successful synthesis of a new class of bis-dihydrazothiazoles as well as three of their transition metal chelates and their use as potential antimicrobials. This report presents the design of some novel hydroxy-tagged bis-dihydrazothiazoles 6a-e and bis-dihydrazothiazolones 9a-e via the reaction of a bis-aldehyde thiosemicarbazone 3 , as a common synthetic precursor, with two groups of hydrazonoyl halide derivatives 4a-e and 7a-e. The chelation affinity of these novel bis-dihydrazothiazoles to behave as neutral tridentate ligands coordinating to the metal ions; Fe(III), Co(II), or Zn(II) through azomethine- N , thiazole- S , and azo- N atoms to form metal complexes with a metal/ligand ratio of 2:1 was confirmed. In-vitro , antimicrobial screening of the novel hydroxy-tagged bis-dihydrazothiazole derivatives, as well as a selected group of their transition metal chelate complexes [M 2 L], was inspected, and the data were measured in comparison to those of ketoconazole and gentamycin as antimicrobial reference standards. Most bis-dihydrazothiazoles 6a-e and bis-dihydrazothiazolones 9a-e showed decent to excellent antimicrobial activities against the screened microbes, but the chloro-substituted bis dihydrazothiazole derivatives 6c and 9c showed exceptional inhibition of Bacillus subtilis (20 mm) , Escherichia coli (25 mm), and Candida albicans (19 mm), and Salmonella typhimurium (19 mm), respectively. Additionally, amongst the three synthesized metal complexes [M 2 L] , only the zinc complex, [Zn 2 L] showed remarkable inhibition of both Staphylococcus aureus (21 mm) and Salmonella typhimurium (19 mm) compared to the reference standard Gentamycin , and was more potent than the free ligand, 6a itself (no activity and 11 mm respectively). Antimicrobial inspection was assessed by the agar well diffusion assay method against all bacterial and fungal strains. Magnetic moment, diffused reflectance, FT-IR, 1H NMR, molar conductivity, thermogravimetric analysis (TGA), X-ray diffraction (XRD), and scanning electron microscope (SEM) were among the many techniques used to elucidate the structures of all novel hydroxy-tagged bis-heterocyclic ligands and their metal chelate complexes. [ABSTRACT FROM AUTHOR]

The aldose reductase (AR) enzyme is an important target enzyme in the development of therapeutics against hyperglycaemia induced health complications such as retinopathy, etc. In the present study, a quantitative structure activity relationship (QSAR) evaluation of a dataset of 226 reported AR inhibitor (ARi) molecules is performed using a genetic algorithm – multi linear regression (GA-MLR) technique. Multi-criteria decision making (MCDM) analysis furnished two five variables based QSAR models with acceptably high performance reflected in various statistical parameters such as, R2 = 0.79–0.80, Q2 LOO = 0.78–0.79, Q2 LMO = 0.78–0.79. The QSAR model analysis revealed some of the molecular features that play crucial role in deciding inhibitory potency of the molecule against AR such as; hydrophobic Nitrogen within 2 Å of the center of mass of the molecule, non-ring Carbon separated by three and four bonds from hydrogen bond donor atoms, number of sp2 hybridized Oxygen separated by four bonds from sp2 hybridized Carbon atoms, etc. 14 in silico generated hits, using a compound 18 (a most potent ARi from present dataset with pIC 50 = 8.04 M) as a template, on QSAR based virtual screening (QSAR-VS) furnished a scaffold 5 with better ARi activity (pIC 50 = 8.05 M) than template compound 18. Furthermore, molecular docking of compound 18 (Docking Score = –7.91 kcal/mol) and scaffold 5 (Docking Score = –8.08 kcal/mol) against AR, divulged that they both occupy the specific pocket(s) in AR receptor binding sites through hydrogen bonding and hydrophobic interactions. Molecular dynamic simulation (MDS) and MMGBSA studies right back the docking results by revealing the fact that binding site residues interact with scaffold 5 and compound 18 to produce a stable complex similar to co-crystallized ligand's conformation. The QSAR analysis, molecular docking, and MDS results are all in agreement and complementary. QSAR-VS successfully identified a more potent novel ARi and can be used in the development of therapeutic agents to treat diabetes. [ABSTRACT FROM AUTHOR]

The urgent need to address the severe environmental risk posed by chromium-contaminated industrial wastewater necessitates the development of eco-friendly cleanup methodologies. Utilizing the Ficus benghalensis plant extracts, the present study aims to develop green zinc oxide nanoparticles for the removal of Cr metal ions from wastewater. The leaves of Ficus benghalensis , often known as the banyan tree, were used to extract a solution for synthesizing ZnO NPs. These nanoparticles were developed with the goal of efficiently eliminating chromium (Cr) from industrial effluents. Batch studies were carried out to assess the efficiency of these synthesized ZnO NPs in treating leather industrial effluent, with aiming for optimal chromium removal. This involved measuring the nanoparticles' capacity to adsorb Cr ions from wastewater samples by comparing chromium levels before and after treatment. Removal efficiency for Cr was estimated through the batches such as optimization of pH, contact time, initial Cr concentration and sorbent dose of ZnO NPs were of the batches. These synthesized ZnO NPs were found to be successful in lowering chromium levels in wastewater to meet permissible limit. The nanoparticles exhibited their highest absorption capacity, reaching 94 % (46 mg/g) at pH 4, with a contact time of 7 hours with the optimum sorbent dose of 0.6 g/L. Hence, the excellent adsorption capabilities of these nanoparticles, together with their environmentally benign manufacturing technique, provide a long-term and efficient solution for chromium-contaminated wastewater treatment. Its novel nature has the potential to significantly improve the safety and cleanliness of water ecosystems, protecting the both i.e. human health and the environment. [Display omitted] • The study synthesizes eco-friendly ZnO nanoparticles from Ficus benghalensis plant extracts. • Techniques such as SEM, EDX, FTIR, UV-Visible spectroscopy, and XRD were used to analyze the synthesized nanoparticles. • Batch experiments evaluated ZnO nanoparticles' effectiveness in adsorbing chromium ions from wastewater. • Optimal conditions for chromium sorption (94 %) were found as pH range of 3–4, contact time of 7 hrs, at a conc. of 46 mg/g. • Nanoparticles offer efficient solution for treating chromium-contaminated wastewater to protect water bodies. [ABSTRACT FROM AUTHOR]

According to the International Diabetes Federation, there will be 578 million individuals worldwide with diabetes by 2030 and 700 million by 2045. One of the promising drug targets to fight diabetes is α-glucosidase (AG), and its inhibitors may be used to manage diabetes by reducing the breakdown of complex carbohydrates into simple sugars. The study aims to identify and validate potential AG inhibitors in natural sources to combat diabetes. Computational techniques such as structure-based virtual screening and molecular dyncamic simulation were employed to predict potential AG inhibitors from compounds of Oroxylum indicum. Finally, in silico results were validated by in vitro analysis using n -butanol fraction of crude methanol extracts. The XP glide scores of top seven hits OI_13, OI_66, OI_16, OI_44, OI_43, OI_20, OI_78 and acarbose were –14.261, –13.475, –13.074, –13.045, –12.978, –12.659, –12.354 and –12.296 kcal/mol, respectively. These hits demonstrated excellent binding affinity towards AG, surpassing the known AG inhibitor acarbose. The MM-GBSA dG binding energies of OI_13, OI_66, and acarbose were −69.093, −62.950, and −53.055 kcal/mol, respectively. Most of the top hits were glycosides, indicating that active compounds lie in the n -butanol fraction of the extract. The IC 50 value for AG inhibition by n -butanol fraction was 248.1 μg/ml, and for that of pure acarbose it was 89.16 μg/ml. The predicted oral absorption rate in humans for the top seven hits was low like acarbose, which favors the use of these compounds as anti-diabetes in the small intestine. In summary, the study provides promising insights into the use of natural compounds derived from O. indicum as potential AG inhibitors to manage diabetes. However, further research, including clinical trials and pharmacological studies, would be necessary to validate their efficacy and safety before clinical use. [ABSTRACT FROM AUTHOR]

Natural product synthesis is an important area of chemical study having various prospects for medicinal, industrial, and agricultural industry. Grignard reaction was developed as a flexible and necessary tool for the production of complex organic compounds in synthetic procedures. Additionally, the synthetic flexibility of the Grignard reaction facilitates its usage in the construction of more complicated ring frameworks and stereoselective transformations. It has been substantially applied in natural product synthesis, demonstrating its effectiveness in the generation of crucial C-C, C-X bonds and the development of intricate molecular structures. Use of Grignard reaction has been significantly studied towards the synthesis of biologically active natural products such as terpenoids, polyketides, alkaloids and amino acids. This review outlines the numerous instances where Grignard reagents have been exploited in the synthesis of notable natural products since past two years. [ABSTRACT FROM AUTHOR]

[Display omitted] N -Arylpyrazoles are important building blocks in many biologically active compounds, natural products, pharmaceuticals, and industries. It is an important moiety of various drugs and exhibits extensive biological activities viz., antibiotic, anticancer, antifungal, anti-inflammatory, anti-coagulant, analgesic, antipyretic, anti-depressant, insecticidal, and hyperglycemic activities. Various protocols have been designed for the synthesis of N -arylpyrazoles facilitated by a wide variety of metal-based catalysts at high or room temperature, metal free reactions, various named reactions, multicomponent reactions, and those occurring under different electromagnetic radiations. Various ligands are found to promote Cu-catalyzed N -arylation of pyrazole under mild conditions in short time. This review describes the synthesis and biological applications of N -arylpyrazole derivatives reported during 2019–2023. [ABSTRACT FROM AUTHOR]

Conventional wastewater treatment technologies tend to be high-capex, energy-intensive solutions that lack specificity for different pollution classes, and do not lend themselves to wide-scale deployment, particularly in areas of the world where industrial wastewater discharge is a significant environmental problem. In tandem, solid waste pollution arising, particularly plastic containing waste, is a persistent and serious pollution issue. This work focuses on the concept of "waste treating waste" and a multidisciplinary effort ranging from materials science and environmental management to sustainable water treatment, in addition to production of graphene oxide from mineral water waste bottles using a simple synthetic procedure that can be economically scaled up for use as a cost-effective adsorbent. Prepared graphene oxide was supported on a polyethersulfone (PES) membrane, and batch filtration studies were performed to examine its performance in the removal of methylene blue (MB) dye, Gentimicin sulphate (GMS) antibiotic, and Na 2 SO 4 and MgSO 4 salts from an aqueous solution. Operating parameters such as initial pollutant concentration, time, and solution pH were investigated and optimized using a response surface methodology (RSM) model. The results confirm the significant efficiency of the filtration process, with a maximum rejection of about 91% for MB, 93% for GMS, 67% for Na 2 SO 4 , and 64% for MgSO 4 , with maximum water flux of 1322, 1367, 1225, and 1059 LMH, respectively. Density functional theory calculations were considered for the GO, PES membrane, and GO/PES membrane with a GGA/PBE optimization level. Adsorption annealing locator analysis was performed for the GO/PES membrane, and the process was recalculated for MB as adsorbate. In conclusion, the adsorption effect employing produced GO/PES membrane is the most important removal, followed by Donnan exclusion and steric hindrance effect. Therefore, it is possible to build new eco-friendly membranes for nanofiltration that are affordable, stable, and effective in removing various pollutants from water systems. [Display omitted] • GO was prepared from PET waste bottles and supported on PES membrane. • Fabricated GO/PES membrane has high porosity, hydrophilicity and negative charged surface. • Rejection of the membrane to the examinant pollutants follow the order of GMS< MB < Na 2 SO 4 < MgSO 4. • DFT predicted adsorption locator MB model with energetic behavior (-48.72 kcal/mol). • Solution pH had the most significant effect on filtration performance. [ABSTRACT FROM AUTHOR]

[Display omitted] A growing interest in pharmacology has made heterocyclic chemistry as one of the emerging branches of organic chemistry. Piperazine is an excellent heterocycle that possesses a large span of pharmaceutical applications. Piperazine derived compounds have shown multiple therapeutic activities such as antioxidant, antibacterial, analgesic, anticancer, antihypertensive, antiallergic, anti-inflammatory, antimalarial, antipsychotic, cardioprotective, antifungal, antidepressant and antiviral. FDA has approved many piperazine scaffold-based drugs for the treatment of various viral infections, therefore establishing the pharmacological importance of piperazine derivatives. Only a few reviews on antiviral activities of piperazine containing compounds are available in the literature, despite of its great medicinal significance. This review deals with piperazine derived compounds as antiviral agents covering the literature reports from 2010 to 2023. [ABSTRACT FROM AUTHOR]

Water contamination can be detrimental to the human health due to higher concentration of carcinogenic heavy metals such as chromium (Cr) in the wastewater. Many traditional methods are being employed in wastewater treatment plants for Cr removal to control the environmental impacts. Such methods include ion exchange, coagulation, membrane filtration, and chemical precipitation and microbial degradation. Recent advances in materials science and green chemistry have led to the development of nanomaterial that possess high specific surface areas and multiple functions, making them suitable for removing metals such as Cr from wastewater. Literature shows that the most efficient, effective, clean, and long-lasting approach for removing heavy metals from wastewater involves adsorbing heavy metals onto the surface of nanomaterial. This review assesses the removal methods of Cr from wastewater, advantages and disadvantages of using nanomaterial to remove Cr from wastewater and potential negative impacts on human health. The latest trends and developments in Cr removal strategies using nanomaterial adsorption are also explored in the present review. • Nanomaterials have great potential for efficient Cr removal from wastewater. • Present work presents major experimental conditions influencing Cr removal and recovery from wastewater. • Efficient nanomaterials on the basis of published publications have been found for effective chromium removal from wastewater. • Adsorption techniques are seen to be preferable to other methods because they ecofriendly, and sustainable. • The optimized chromium removal conditions used on this topic are compiled here. [ABSTRACT FROM AUTHOR]

Imidazothiadiazole is a fundamental fused heterocyclic compound containing imidazole and thiadiazole ring systems. This versatile framework has significant applications in pharmaceutical chemistry and also possessed a remarkable biological profile. The derivatives of imidazo[2,1-b][1,3,4]thiadiazole have a broad spectrum of biological applications such as antitumor, tubulin inhibitor, anticancer, antifungal, anti-inflammatory, antimicrobial, antitubercular, anticonvulsant, antibacterial and as enzyme inhibitors. These derivatives also play a significant role in the development of non-linear optics and photo-electronics. Synthesis of this fused bicyclic compound mainly involved the reaction between 2-amino-1,3,4-thiadiazoles and α-haloketones, with different substitutions at the 2, 5, and 6 positions of the ring system. Moreover, microwave assisted multicomponent and C–C coupling reactions in the presence of catalysts or under solvent free reaction conditions were found to be reliable and valuable approaches. This review is a concerted approach to describe the synthesis and applications of imidazo[2,1-b][1,3,4] thiadiazole derivatives reported during 2015–2022. [ABSTRACT FROM AUTHOR]

[Display omitted] • QSAR study of structurally diverse molecules with experimentally reported EC 50 against SARS CoV-229E 3CLpro. • Identification of novel hit with improved pEC 50. • Molecular docking analysis pointed out crucial interaction of hit with key amino acid residues of the target protein. • MDS analysis strengthened the results of docking analysis by indicating the formation of a stable complex. • MMGBSA calculation support the MD simulation and docking results. Congruous coronavirus drug targets and analogous lead molecules must be identified as quickly as possible to produce antiviral therapeutics against human coronavirus (HCoV SARS 3CLpro) infections. In the present communication, we bear recognized a HIT candidate for HCoV SARS 3CLpro inhibition. Four Parametric GA-MLR primarily based QSAR model (R2:0.84, R2adj:0.82, Q2loo: 0.78) was once promoted using a dataset over 37 structurally diverse molecules along QSAR based virtual screening (QSAR-VS), molecular docking (MD) then molecular dynamic simulation (MDS) analysis and MMGBSA calculations. The QSAR-based virtual screening was utilized to find novel lead molecules from an in-house database of 100 molecules. The QSAR-vS successfully offered a hit molecule with an improved P EC 50 value from 5.88 to 6.08. The benzene ring, phenyl ring, amide oxygen and nitrogen, and other important pharmacophoric sites are revealed via MD and MDS studies. Ile164, Pro188, Leu190, Thr25, His41, Asn46, Thr47, Ser49, Asn189, Gln191, Thr47, and Asn141 are among the key amino acid residues in the S1 and S2 pocket. A stable complex of a lead molecule with the HCoV SARS 3CLpro was discovered using MDS. MM-GBSA calculations resulted from MD simulation results well supported with the binding energies calculated from the docking results. The results of this study can be exploited to develop a novel antiviral target, such as an HCoV SARS 3CLpro Inhibitor. [ABSTRACT FROM AUTHOR]

[Display omitted] Two new series of bis- thiazoles 6a-f and bis- thiazolones 9a-d were prepared via reacting bis-thiosemicarbazone 3 with hydrazonoyl chloride derivatives 4a-f and 7a-d , respectively, in dioxane under basic conditions. Another group of bis- thiazole derivatives 12a-h was prepared by reacting bis-thiosemicarbazone 3 with each of phenacyl bromide derivatives 10a-h under a similar reaction protocol. A plausible mechanism was proposed. Structural elucidation of the new products was established using both elemental and spectrometric/spectroscopic analyses. Structural, electronic, and the pharmacological characteristics of the prepared molecules were investigated with DFT calculations. Antibacterial and antifungal activities of the new bis- thiazoles were screened and compared with vancomycin and amphotericin B as antimicrobial standards. Molecular docking studies on the promising candidate compounds, with the lowest minimum inhibitory concentrations (MIC), were performed with SAP2 of C. albicans and FabI of S. aureus and P. aeruginosa. [ABSTRACT FROM AUTHOR]