Computational discovery of potential human carbonic anhydrase IX inhibitors

This study explores the potential of nitro compounds as inhibitors of Carbonic Anhydrase IX (CAIX) for cancer therapy. Molecular docking and virtual screening were employed to identify lead molecules, focusing on their binding affinities and interactions with CAIX. Six compounds, namely D1 (-8.295 kcal/mol), D2 (-10.980 kcal/mol), D3 (-10.963 kcal/mol), D4 (-7.170 kcal/mol), D5 (-7.368 kcal/mol), and D6 (-8.705 kcal/mol), were selected based on their promising docking scores and Molecular Mechanics-Generalized Born Surface Area (MMGBSA) results. Molecular dynamics simulations further confirmed the stability of the CAIX-lead compound complexes, with low root-mean-square deviation (RMSD) values and minimal fluctuations in protein and ligand structures. The analysis of root-mean-square fluctuations (RMSF) highlighted the overall stability of these complexes, with localized fluctuations. Detailed investigation of protein-ligand contact dynamics unveiled strong and consistent interactions, including hydrogen bonds, ionic interactions, water bridges, and salt bridges. These novel interactions shed light on the dynamic behavior of the CAIX-lead compound complexes. Briefly, this study establishes a robust framework for advancing D1, D2, and D3 as promising CAIX inhibitors in cancer treatment. The meticulous analysis and comprehensive approach applied to these primary compounds yield substantial insights into their potential as therapeutic agents, setting the stage for forthcoming experimental validation and clinical utilization.