SYNTHESIS, IN-SILICO DESIGN, ADMET PROFILING, AND DOCKING STUDIES OF BENZOHYDRAZIDE DERIVATIVES AS POTENTIAL ANTI-BACTERIAL AGENTS

Abstract

A novel series of benzohydrazide derivatives, including Schiff base analogs (S1–S6), were synthesized and structurally validated using TLC, melting point analysis, and IR spectroscopy. In-silico ADMET analysis via SwissADME and Deep.Pk indicated favorable drug-likeness, with no Lipinski violations, good oral bioavailability (≥0.55), high intestinal absorption, and blood-brain barrier permeability. Metabolic profiling showed varied interactions with cytochrome P450 enzymes and BCRP, where the compounds acted as both inhibitors and substrates. All compounds exhibited short half-lives (5.34–9.54 h) and acceptable clearance rates (<3 h). Toxicity predictions indicated no mutagenicity (AMES test) and good biodegradability; however, compound S2 showed potential carcinogenicity, respiratory toxicity, and a risk of drug-induced liver injury (DiLi).

Molecular docking using AutoDock Vina 4.2 revealed moderate to good antibacterial activity, with binding scores ranging from –6.8 to –7.7 kcal/mol, comparable to ciprofloxacin (–7.8 kcal/mol) and irinotecan (–8.5 kcal/mol). Structure-activity relationship (SAR) analysis emphasized the importance of electron-donating and electron-withdrawing groups, the Schiff base functionality, and aromatic modifications in improving both binding affinity and pharmacokinetic profiles. Overall, the benzohydrazide scaffold demonstrated promising antibacterial potential and warrants further investigation for antiviral, antioxidant, and anti-tubercular applications through in-vitro and in-vivo studies.