Mechanistic insights into antioxidant and antibacterial effects of indole-pyrazole-carbohydrazide hybrids through density functional theory, docking, and molecular dynamics studies

A new series of indole-pyrazole-carbohydrazide derivatives ( IH-1-IH-5 ) was synthesized through acid-catalyzed condensation of 1H-indole-5-carbaldehyde with substituted pyrazole-5-carbohydrazides, aiming to develop multifunctional antioxidants and antibacterials. In2,2′-diphenyl-1-picrylhydrazyl (DPPH) assays, electron-donating IH-3 (methoxy, IC 50 0.027 mg/mL) and IH-2 (methyl, 0.029 mg/mL) excelled, correlating with narrow band gaps (3.95–4.08 eV), high softness, and nucleophilicity from density functional theory (DFT) at B3LYP/6-31G(d,p); halogenated IH-4/5 were moderate. Antibacterial screening against B. cereus , S. aureus , K. pneumoniae , and E. coli showed IH-5 (bromo, zones up to 33 mm) and IH-4 (chloro) most potent, supported by GyrB docking (-10.59 kcal/mol), stable 100ns molecular dynamics (ΔG -16.53 kcal/mol for IH-2 ), and Lipinski-compliant optimization and theoretical biological analyses revealed substituent-driven electron-donors boosting antioxidant, halogens enhancing antibacterial interactions-positioning these as promising therapeutic leads.