Comprehensive study of Biginelli's compounds show antibacterial activity against Vibrio parahaemolyticus of two strains: In vitro and computational approaches

Abstract

This study addresses the critical challenges faced by global aquatic industries such as overfishing, habitat destruction, pollution, climate change, and unsustainable aquaculture practices. It focuses on developing effective solutions by synthesizing potent inhibitors against Vibrio parahaemolyticus of two strains namely: MTCC-451 (A) and Vp-S14 (B). Biginelli's compounds (B1-4) were identified as promising inhibitors with confirmed antibacterial activity through in silico and in vitro studies. Then virtual screening through ADMET, best correlation with regard to QSAR studies, the docking analysis is used to determine, the ligand B1 would be more favorable comparable with others for conducting bacterial studies and DFT calculations show that the optimized structure of ligand B1 has the best FMO values, MEP values and appropriate electronic structural state. This research study is very helpful and matches for "Antibacterial analysis". A total of 99 Biginelli compounds were selected for virtual screening including 2D-QSAR, ADME/T, molecular docking, and DFT calculations. The virtual screened compounds were synthesized then for biological studies. The four highlighted compounds (B1-4) with favorable ADME properties and strong binding affinities compared to gentamicin in both ADME and docking analysis respectively. Further analysis via DFT provided structural insights and active site identification. In vitro assays against pathogenic Vp strains demonstrated significant bactericidal activity, with MIC values of 1.25 mg/ml (MTCC-451) and 1 mg/ml (Vp-S14).

Keywords: ADME/T; Antibacterial drug; Biginelli's compounds; DFT calculations; In silico, 2D-QSAR; Molecular docking; Vibrio parahaemolyticus.