02579nas a2200289   4500008004100000022001400041245013400055210006900189260000900258300001000267490000700277520160400284653002201888653003001910653001601940653001401956653001301970100002501983700002202008700002302030700002002053700002802073700002502101700001502126700002202141856012602163       2025                        eng d  a2045-232200aSynthesis, characterization, computational and biological evaluation of pyrazole hydrazones as promising anti-inflammatory agents0 aSynthesis characterization computational and biological evaluati  cNOV   a422060 v153 a<p>
	In this study, two pyrazole-based hydrazone derivatives, 5-methyl-1-phenyl-4-(1-(2-phenylhydrazineylidene)ethyl)-1H-pyrazole (PMPH) and 1-(4-fluorophenyl)-5-methyl-4-(1-(2-phenylhydrazineylidene)ethyl)-1H-pyr azole (4F-PMPH), were synthesized and the structures of the compounds were elucidated through FT-IR, 1H and 13C NMR, and mass spectral methods. The anti-inflammatory potential was evaluated using the bovine serum albumin denaturation assay, with PMPH and 4F-PMPH showing maximum inhibition at 0.5 mg/mL, respectively, suggesting that fluorine substitution enhances bioactivity. Molecular docking studies against COX-II (PDB: 3LN1) revealed favorable binding energies of - 7.21 kcal/mol (PMPH) and - 8.03 kcal/mol (4F-PMPH). Molecular dynamics simulation of the best docked compound 4F-PMPH with COX-II (PDB: 3LN1) revealed a stable complex over a 100 ns simulation, supporting its potential as a promising inhibitor. In silico ADME analyses revealed pharmacokinetic behavior and drug-likeness. A comparative Density functional theory-based spectroscopic and electronic investigation was conducted using the B3LYP/6-31G(d,p) level of theory. Vibrational frequency analysis showed strong correlation between theoretical and experimental IR spectra. Frontier molecular orbital analysis, molecular electrostatic surface potential maps, Mulliken charges, electronic and global reactivity parameters were also studied. Besides, reduced density gradient, non-covalent interaction, electron localization function, and localized orbital locator maps were analyzed for both the compounds.</p>
10aAnti-inflammatory10aDensity functional theory10aDrug design10aHydrazone10aPyrazole1 aDeshmukh, Hemant, S.1 aAdole, Vishnu, A.1 aFrit, Alfind, Paul1 aMali, Suraj, N.1 aYasin, Haya, Khader Ahm1 aPatil, Bhausaheb, N.1 aJanani, S.1 aJagdale, Bapu, S.  uhttps://library.ncl.res.in/content/synthesis-characterization-computational-and-biological-evaluation-pyrazole-hydrazones