Synthesis, in silico Biological and ADMET Predictions, and Molecular Docking of Isatin Schiff Base Derivatives as Promising Antituberculosis Agents

Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis, continues to be a global health challenge, particularly with the rise of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. In this study, five isatin Schiff base derivatives were designed, synthesized, and evaluated using in silico approaches to identify potential antitubercular agents. The ADMET profiles of isatin Schiff base derivatives were studied via pkCSM, admetSAR, and SwissADME servers. Biological activity predictions were conducted using the PASS online tool, with significant activity considered at Pa > 0.7. Molecular docking studies were performed using MOE software targeting the InhA enzyme (PDB ID: 4TZK), a key protein in the fatty acid synthesis pathway of Mycobacterium tuberculosis. The docking results revealed that all five ligands exhibited favorable binding affinities and strong interactions with the enzyme’s active site. Additionally, the ADMET profiles suggested good drug-likeness and acceptable pharmacokinetic behavior. These findings suggest that the synthesized isatin Schiff base derivatives (A1–A5) are promising candidates for further development as antitubercular agents. Conclusion: This study demonstrated that the five isatin Schiff base derivatives (A1–A5) show strong potential as antitubercular agents. Molecular docking revealed promising interactions with the InhA enzyme, especially for ligand A5. ADMET studies analyses further supported their drug-likeness and biological activity. These findings warrant further experimental validation and optimization.