DESIGN, SYNTHESIS, AND DOCKING STUDIES OF PYRIDINE-SULFONAMIDE THIAZOLE INDOLE DERIVATIVES FOR POTENTIAL BIOLOGICAL APPICATION

This study presents an in silico molecular docking analysis of heterocyclic compounds 35a–35l and their modular derivatives targeting tubulin proteins from two pathogens: Pseudomonas sp. ADP (PDB ID: 6C6G, for antimicrobial activity) and Candida albicans SC53114 (PDB ID: 7RJC, for antifungal activity). The goal was to evaluate binding affinities and conformational stability of nitrogen-containing compounds using predicted binding energies and RMSD values relative to both unbound and lowest-energy bound conformations. Among all compounds, Compound 35a Module 1 showed the strongest binding affinity (−16.6 kcal/mol) with no deviation (RMSD = 0), indicating high binding stability. Compound 35b also demonstrated promising results, with several modules exhibiting affinities below −14.0 kcal/mol; however, high RMSD values in some modules suggested less stable or alternative binding modes. In contrast, Compounds 35c, 35k, and 35l had lower binding affinities (−6.6 to −8.0 kcal/mol), indicating weaker interaction with the target protein. Docking results against 7RJC highlighted Compound 35f Module 1 and Compound 35k Module 1 as potential antifungal leads, showing binding affinities of −14.1 and −15.9 kcal/mol, respectively, with minimal RMSD values. Overall, structural modifications among the modules were found to significantly influence binding strength and pose stability. These findings provide valuable insight for optimizing the physicochemical properties and biological activity of nitrogen-containing heterocycles in the development of antimicrobial and antifungal agents.