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 µg/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.