02453nas a2200289 4500008004100000022001400041245013400055210006900189260000800258300001500266490000700281520151600288653000601804653002201810653002301832653002401855653002101879653001301900100001901913700001701932700002101949700001701970700002201987700001902009700001702028856011802045 2025 eng d a2365-654900aSynthesis, biological screening, and molecular docking of hybrid pyrazole scaffolds for antitubercular and antimicrobial activity0 aSynthesis biological screening and molecular docking of hybrid p cJAN ae2024048300 v103 a

This study reports the synthesis, characterization, and docking analysis of 21 novel compounds, including asymmetric dihydropyridines (4a-4o) and chalcones (6a-6f), derived from coupling 1,3-(substituted)-diphenyl-1H-pyrazole-4-carbaldehyde with active methylene compounds and 3-acetyl-4-hydroxycoumarin, respectively. Structural confirmation was achieved through 1H and 13C NMR, IR, and mass spectrometry. Biological screening against mycobacterium tuberculosis H37Ra identified compounds 4b, 4d, 4f, 4g , 4i, 4k, 6e, and 6f as significant antitubercular agents. Antibacterial evaluation at 30 mu g/mL showed selective inhibition of gram-positive bacteria, with compound 6e active against Staphylococcus aureus and Bacillus subtilis, and 6f showing activity specifically against S. aureus. Docking studies indicated effective InhA binding (Delta G = -3.52 to -7.27 kcal/mol) and inhibition constants ranging from 2640 to 4.71 mu M. Key binding interactions with residues TYR156 and ILE192 were observed, enhancing affinity, particularly for compound 6e. The SAR analysis emphasized the enhanced antitubercular potency of 2-chloroacetyl and 2,4-dichlorobenzoyl substitutions in the dihydropyridine series, while in the chalcone series, specific substitutions, such as the 3-nitro substitution in 6e, enhance antitubercular and antimicrobial potency due to stronger hydrogen bonding and increased polar surface area, while the 4-fluoro substitution in 6f confers selective activity against S. aureus.

10a110a4-dihydropyridine10a4-hydroxy coumarin10aBiological activity10aIn silco studies10aPyrazole1 aBavishi, Abhay1 aVala, Hardev1 aRadadiya, Ashish1 aSwami, Sagar1 aThakrar, Shailesh1 aSarkar, Dhiman1 aShah, Anamik uhttps://library.ncl.res.in/content/synthesis-biological-screening-and-molecular-docking-hybrid-pyrazole-scaffolds