Synthesis of Isatin-Schiff Base and 1,2,3-Triazole Hybrids as Anti-SARS-CoV-2 Agents: DFT, Molecular Docking, and ADMET Studies

This study focuses on discovering novel antiviral compounds to address challenges posed by viral mutations and drug resistance. In this work, 3-((3,5-dimethylphenyl)imino)-1-((1-substituted-1H-1,2,3-triazol-4-yl)methyl)indolin-2-one derivatives 16–21 were synthesized via two distinct routes. The first route involved click cycloaddition reactions of Schiff base 3 with various substituted azides, while the second utilized the condensation of pre-synthesized isatin hybrids 10–15 with 3,5-dimethylaniline. The structures of these newly synthesized compounds were confirmed using advanced spectroscopic techniques and elemental analysis. Furthermore, in vitro evaluations included cytotoxicity and antiviral assays against SARS-CoV-2. Cytotoxicity was assessed using crystal violet assays to determine the cytotoxic concentration (CC50) of the compounds on Vero E6 cells. Antiviral activity was also evaluated. Among the tested compounds, compound 21 exhibited moderate antiviral activity, with a CC50 of 135.3 µM and an IC50 of 44.1 µM, resulting in a safety index (SI) of 3.1. Computational studies such as molecular docking, DFT calculations, molecular dynamics simulations, and drug-likeness assessments confirmed the stability, favorable pharmacokinetics, and drug-like properties of compound 21. These findings highlight the promise of these compounds as candidates for further optimization and development as antiviral agents.