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Series of indole‐1,3,4‐thiadiazole compounds (IT 1–7) were synthesized and characterized by FT‐IR, 1H NMR, 13C NMR and ESI‐MS spectral data. Further, the compounds (IT 1–7) were screened for antidiabetic, antioxidant and anti‐inflammatory activities. Most of these compounds exhibited moderate to good antidiabetic, antioxidant and anti‐inflammatory activities against α‐amylase enzyme, ABTS and lipoxygenase enzyme, respectively. Among these, IT‐1 displayed the better activity compared to that of standard drugs. The mechanism of binding of IT‐1, IT‐5 and IT‐6 with a transporter protein, human serum albumin was investigated by fluorescence spectroscopic and circular dichroism studies. These compounds quenched the intrinsic fluorescence intensity of HSA and moderate binding was evident from the values of binding constants which are in the order of 105 M−1. The molecular docking studies of the compounds were performed against human pancreatic alpha‐amylase in complex with montbretin A (PDB ID: 4W93). The studied compounds interacted with amino acid residues (ASP197, GLU240 and TYR151) which were similar to that of the reference drug, acarbose. The ADME properties of designed compounds were studied using SwissADME software. All the compounds obeyed Lipinski's rule of five. All the compounds showed low or non‐toxicity towards different toxicity classes as analyzed using ProTox‐II online tool. [ABSTRACT FROM AUTHOR]

In this study, new series of N'-(2-(substitutedphenoxy)acetyl)-4-(1H-pyrrol-1-yl)benzohydrazides (3a-j) 4-(2,5-dimethyl-1H-pyrrol-1-yl)-N'-(2-(substitutedphenoxy)acetyl)benzohydrazides (5a-j) were synthesized, characterized and assessed as inhibitors of enoyl ACP reductase and DHFR. Most of the compounds exhibited dual inhibition against the enzymes enoyl ACP reductase and DHFR. Several synthesized substances also demonstrated significant antibacterial and antitubercular properties. A molecular docking analysis was conducted in order to determine the potential mechanism of action of the synthesized compounds. The results indicated that there were binding interactions seen with the active sites of dihydrofolate reductase and enoyl ACP reductase. Additionally, important structural details were identified that play a critical role in sustaining the dual inhibitory activity. These findings were useful for the development of future dual inhibitors. Therefore, this study provided strong evidence that several synthesized molecules could exert their antitubercular properties at the cellular level through multi-target inhibition. By shedding light on the mechanisms through which these compounds exert their inhibitory effects, this research opens up promising avenues for the future development of dual inhibitors with enhanced antibacterial and antitubercular properties. The study's findings underscore the importance of multi-target approaches in drug design, providing a strong foundation for the design and optimization of novel compounds that can effectively target bacterial infections at the cellular level. [ABSTRACT FROM AUTHOR]

We present a study on a new class of Schiff bases with pyrimidine linked hydrazinyl azole backbone. These compounds were synthesized using conventional and ultrasonication methods. Our design strategy incorporated three heteroaromatic azoles and various substituents on the pyrimidine scaffold to enhance antimicrobial properties. Antibacterial and antifungal screenings were conducted against specific pathogens, and molecular docking studies supported the results. The compounds exhibited significant antimicrobial activities, particularly against K. pneumoniae, surpassing the standard drug. These Schiff bases hold promise as potential antimicrobial agents. [ABSTRACT FROM AUTHOR]

In the present work, Fe3O4 nanoparticles were prepared by the co‐precipitation method and employed as effective nanocatalysts in the tandem synthesis of 3‐(4,5‐diaryl‐1H‐imidazol‐2‐yl)quinolin‐2‐amines. An effective multicomponent reaction is plighted for 2‐chloroquinoline‐3‐carbaldehydes and substituted benzils to obtain novel heterocycles 3‐(4,5‐diaryl‐1H‐imidazol‐2‐yl)quinolin‐2‐amines. These molecules are fluorescent and hence for proper understanding of optical behaviour, solvatochromic and DFT studies were carried out. Also, the optical and energy bandgaps were calculated. Molecular docking studies manifested the strong binding affinities by these compounds at the active site of the Candida albicans dihydrofolate reductase enzyme (PDB ID: 1AI9) and Novobiocin (PDB ID: 4URO) with excellent C‐score values. Antimicrobial activity screening results have shown remarkable activity against Escherichia coli with appreciable MIC values and hence noteworthy action has been demonstrated against this bacterium. The zones of inhibition for some of the target compounds are also good against gram positive Staphylococcus aureus exhibiting excellent activity. [ABSTRACT FROM AUTHOR]

Using 2-(9H-fluoren-9-ylidene)hydrazinyl)thiazol-4(5H)-one and substituted benzaldehydes, a new library of fluorenone–thiazolidine-4-one scaffolds (5a–u) were synthesized and characterized using FT-IR, 1H NMR, 13C NMR and mass spectral data. Single crystals of compound 5s were developed and crystallographic data were collected. Hirshfeld surface evaluation was used to investigate the intermolecular interactions that exist within the crystals. The synthesized compounds were screened for in vitro antioxidant and anti-diabetic properties by DPPH scavenging activity and α-glucosidase inhibition, respectively. Compounds 5a–l exhibited promising DPPH scavenging activity. Compound 5l showed an IC50 value of 27.70 ± 0.8 μM, which is 4.25-fold greater as compared to that of the standard, gallic acid (an IC50 value of 117.92 ± 2.8 μM). Compound 5g exhibited good α-glucosidase inhibition with an IC50 value of 114.58 ± 1.6 μM, which is less than that of the standard inhibitor, acarbose, with an IC50 value of 115.49 ± 2.2 μM. The mechanism of binding of compound 5g with human serum albumin (HSA) and calf thymus DNA (Ct-DNA) was studied by fluorescence spectroscopy. Furthermore, the ADME properties of the designed compounds were studied using the SwissADME online tool. The molecular docking studies of the compounds were performed against acid-α-glucosidase, in complex with 1-deoxynojirimycin (PDB ID: 5NN5). [ABSTRACT FROM AUTHOR]

A proficient copper(I) catalyzed three-component synthetic protocol has been established for the synthesis of medicinally essential substituted imidazo[1,2-a]pyridines by means of C–H bond amination followed by acetylene incorporation under microwave irradiation. The biological results and computational analysis suggested that the compounds had a greater affinity for the COX-2 enzyme than for the COX-1 enzyme. The investigation of docked (PDB ID: 5IKR ; A-chain) postures of the compounds exemplified that they embrace similar configurations to the exceedingly selective COX-2 inhibitor. The compounds 8e, 8h, 8l, 8n, 8p, 8r, 8t, 8v and 8x originated as the most efficient and selective COX-2 inhibitors with IC50 values of 18.94, 0.02, 3.28, 0.067, 0.05, 19.42, 3.66, 0.19 and 24.59 μg mL−1 respectively in contrast to mefenamic acid (25.74 μg mL−1). The selectivity index was obtained for all the significantly active molecules. Excitingly, the molecules that were effective as COX-2 inhibitors were active as antioxidant agents as well. [ABSTRACT FROM AUTHOR]

In this study, a new series of 4-(2,5-dimethyl-1H-pyrrol-1-yl)-N′-(2-(substituted)acetyl) benzohydrazides (5a–n) were prepared and new heterocycles underwent thorough characterization and evaluation for antibacterial activity; some of them underwent further testing for in vitro inhibition of enoyl ACP reductase and DHFR enzymes. The majority of the synthesized molecules exhibited appreciable action against DHFR and enoyl ACP reductase enzymes. Some of the synthesized compounds also showed strong antibacterial and antitubercular properties. In order to determine the potential mode of action of the synthesized compounds, a molecular docking investigation was conducted. The results revealed binding interactions with both the dihydrofolate reductase and enoyl ACP reductase active sites. These molecules represent excellent future therapeutic possibilities with potential uses in the biological and medical sciences due to the compounds' pronounced docking properties and biological activity. [ABSTRACT FROM AUTHOR]

A new class of bis(azolyl) pyridine‐2,6‐dicarboxamides based derivatives were designed and synthesized by employing ultrasonication methodology. In this work, we studied the role of different heteroaromatic azole units such as oxazole, thiazole and imidazole moieties along with different donating/withdrawing substituents on the pyridine scaffold and anticipated to display good biological activities. The detailed molecular docking studies validates the antimicrobial activities of these targeted molecules. Further, to evaluate their antioxidant properties, the target compounds were exposed to three different invitro free radical scavenging assay methods. Further, using the disc diffusion method, the targeted molecules were screened for invitro antibacterial activities against the pathogenic stains. Besides, the targeted molecules were also tested against A. niger and P. chrysogenum strains to assess their antifungal activity. The screening results reveals that, the most of the compounds form the series demonstrating reasonable to decent antioxidant and antimicrobial activities against pathogenic stains in comparison with the standard drug. [ABSTRACT FROM AUTHOR]

The 2-substituted benzoxazole derivatives are known to exhibit a wide spectrum of biological potential. Two series of novel benzoxazole derivatives containing 2-phenyl and 2-N-phenyl groups were synthesized, by following the green chemistry approach. All the newly synthesized derivatives were screened against gram-positive bacteria (Streptococcus pyogenes, Staphylococcus aureus), gramnegative bacteria (Pseudomonas aeruginosa, Escherichia coli) and the fungus (Aspergillus clavatus and Candida albicans). Most of these compounds have demonstrated potent antibacterial activities, especially against E. coli at 25 μg/mL, along with moderate antifungal activity. Among these, two compounds, 21 and 18, showed interesting antibacterial profile. Molecular docking studies suggested that the antibacterial activity can be linked to the inhibition of DNA gyrase. Overall, the study proposes that these biologically potent compounds can be considered for developing the next generation antimicrobial agents. [ABSTRACT FROM AUTHOR]

A series of new Coumarin hydrazone oxime scaffolds were synthesised as potential anti‐TB agents. The structures of the scaffolds were confirmed by spectroscopic and analytical techniques. X‐ray crystallography confirmed the structure of compound 6‐methyl‐4‐((((Z)‐((E)‐3‐(2‐phenylhydrazono)butan‐2‐ylidene)amino)oxy)methyl)‐2H‐chromen‐2‐one (5a). The coumarin hydrazone oxime scaffolds were tested in‐vitro against the Mycobacterium tuberculosis H37Rv strain, and Vero cells were used to assess cytotoxicity. Compound 5b was obtained as the hit candidate, exhibiting MIC 0.78 μg/mL, showing more potent anti‐TB activity than Rifamycin and comparable activity to Isoniazid. There was minimal cytotoxicity observed against Vero cells for the most active compounds, indicating a good safety‐profile.In addition, the most diligent compound 5b demonstrated substantial binding interactions at the PDB:4DQU enzyme's active site and also displayed greater C‐score value than that of 4DQU ligand which validates the observed results. [ABSTRACT FROM AUTHOR]