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Objective: The tandem Knoevenagel-cyclocondensation reaction of aromatic aldehydes, malonitrile, and phenylhydrazine in water and ethanol at room temperature is described as an effective, one-pot, threecomponent synthesis of many scientifically relevant heterocyclic compounds. Methods: As a part of our efforts, we have synthesized pyrazole-4-carbonitriles and characterized using various spectroscopic methods and subjected for antimicrobial analysis. Results and Discussion: From our analysis, we observed best in vitro candidate as 5-amino-3-(2,5-difluorophenyl)-1-phenyl-1H-pyrazole-4-carbonitrile. The molecular docking analysis on common bacterial target suggested the involvement of 2,2-dialkylglycine decarboxylase (PDB ID: 1D7U) as a target for compound (IVi) (docking score: –9.32 kcal/mol). Furthermore, a molecular dynamic simulation of 100 ns resulted in the stability of best docked candidate, (IVi): 1D7U. Conclusions: We propose that best docked candidate, (IVi) as potential antimicrobial agents. [ABSTRACT FROM AUTHOR]

A series of polysubstituted imidazoles were synthesized in good yields by employing stable and active silica-OSO3H catalyst via a one-pot four-component approach. This new protocol has the advantages of inexpensive, nontoxic, and heterogeneous catalyst along with mild reaction conditions, short reaction times, and easy workup and purification procedures, which enhance its practicality. The synthesized imidazoles were subjected to molecular docking with some bacterial target enzymes (PDB IDs: 1KZN, 1BAG, 1D7U, 2XCT). Compounds 1k, 1e, 1o, and 1i showed the best docking scores on selected targets, –8.2, –8.4, –8.5, and –9.3 kcal/mol, respectively. Antibacterial evaluation of the synthesized compounds against S. aureus, B. subtilis, E. coli, and K. pneumoniae revealed their potential activity with MIC values of 64 to 100 µg/mL. Imidazoles containing another heterocyclic unit such as pyridyl or thienyl (1d, 1f, 1h, and 1m) showed better antibacterial activity than other analogues. [ABSTRACT FROM AUTHOR]

A new design of thiazolidin-4-one derivatives were evaluated for their cytotoxicity on CHO (Chinese Hamster ovary cells), SKOV3 (Human Ovarian cancer) and HeLa (Human cervical) cancer cell lines. All these compounds exhibited moderate cytotoxicity against CHO cells but showed potent anticancer activity against both SKOV3 and HeLa cell lines. A high antiproliferative activity of compound (Va), (Vd) and (Vm) against SKOV3 and (Va), (Vm) and (Vq) against HeLa cell lines were observed. It is interesting to note that (Vq) and (Vc) are comparatively lesser toxic to the normal CHO cells but highly cytotoxic against HeLa and SKOV3 cells. In the antimicrobial activity (Vb), (Vc) and (Vq) compounds displayed a moderately antifungal activity against Aspergillus niger and A. flavus at 150 μg/mL concentration. Moreover, molecular docking and molecular dynamics analysis over 100 ns with target FGFR2 (4j96): (Vq) retained good acceptable profiles for stability of this complex. Based on these bioactivity studies, it is indicated that (Vb) and (Vq) compounds can be potential substitutes for the treatment of ovarian and cervical cancer respectively because of their high specificity to both types of ovarian and cervical cancers with minimal toxicity to normal cells. [ABSTRACT FROM AUTHOR]