Design, synthesis and in silico molecular modelling studies of 2-Hydrazineyl-2-oxoethyl-4-(1H-pyrrol-1-yb) benzoate derivatives: a potent dual DHFR and ENR-reductase inhibitors with antitubercular, antibacterial and cytotoxic potential.

ABSTRACT: The current research includes the study of 28 new 2-hydrazineyl-2-oxoethyl-4-(1H-pyrrol-1-yl) benzoate derivatives as antitubercular, antibacterial, and enoyl-ACP reductase enzyme inhibitors. SYBYL-X.2.0 was used to investigate the molecular docking of ENR-ACP reductase/InhA in complex with 1-cyclohexyl-N-(3,5-dichlorophenyl)-5-oxopyrrolidine-3-carboxamide (PDB ID:4TZK) and MtDHFR in complex with methotrexate (PDB ID:1DF7). All of the reported derivatives have two or more H-bonding interactions with TYR158 and the cofactor NAD + , which fit snugly into InhA's binding pocket, with MIC values of 0.8-3.12 µg/mL, 0.4-3.12 µg/mL, and 1.6-12.5 µg/mL [4(a-e), 5(a-p), 6(a-e)]. Also, the molecular H-bonding interactions of reported molecules with amino acids ARG32 and ARG60 of MtDHFR showed the int

SUBMITTER: Mahnashi MH 

PROVIDER: S-EPMC12088000 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature