Discovery of Novel Isatin Encompassing Oxadiazoles as Potential Inhibitors against New Delhi Metallo-β-lactamase-1: Synthesis, Spectral Analysis, Antimicrobial, and Molecular Modeling Studies

Objective: Efficient synthesis of isatin Schiff's bases (IIIa-IIId) and isatin-derived 1,3,4-oxadizoles (IVa-IVd) and evaluation of their in vitro antibacterial, antifungal, and anti-TB activities. The molecular docking studies were performed with protein New Delhi Metallo-Beta-lactamase-1 and Mycobacterium tuberculosis enoyl reductase and molecular dynamics simulation. Methods: The chemical structures were confirmed by IR, NMR, and mass spectroscopic techniques. The biological screenings were studied for the foresaid compounds for their in vitro antibacterial, antifungal, and anti-TB activity using MIC method. Molecular docking and dynamics simulation studies were conducted using AutoDock software with proteins New Delhi Metallo-Beta-lactamase-1 (NDM-1, PDB ID: 3ZR9) and Mycobacterium tuberculosis enoyl reductase (INHA, PDB ID: 4TZK). Results and Discussion: The compounds (IVa-IVc) displayed excellent in vitro antimicrobial activity. Also, the compounds (IVa-IVc), were found to be most active with a MIC of 3.125 mu g/mL. For the docked proteins, all the compounds exhibited a substantial binding affinity. Further, molecular dynamics were disclosed for compounds (IVa-IVc). Conclusions: The compounds (IIIa-IIId) and (IVa-IVd) were synthesized from substituted isatins, p-amino benzoic acid, and isoniazid with moderate to excellent yields. These reactions are simple, convenient, and hitherto novel. In docking studies the compounds (IVa-IVc) showed excellent bind affinity towards the enzymes.