In silico study of thiazole-based amino coumarin derivatives with promising carbonic anhydrase inhibitory activity.

OBJECTIVE: Aim: In this study, a series of novel aminocoumarin derivatives incorporating an amino-thiazole moiety were designed to evaluate their inhibitory activity against the carbonic anhydrase IX enzyme (PDB ID: 6fe0) and to explore their potential anti-neoplastic properties through molecular docking analysis. PATIENTS AND METHODS: Materials and Methods: Molecular docking was performed using the Molecular Operating Environment (MOE) software, version 2015.10. The Standard Score (S-score) and Root Mean Square Deviation (RMSD) parameters were used to evaluate the binding affinities of the ligands toward the target enzyme. RESULTS: Results: The four synthesized ligands (IIIa, IIIb, IIIc, and IIId) demonstrated stronger binding affinities to carbonic anhydrase IX compared with the reference ligand, acetazolamide. Among them, compound IIId showed the most favorable binding profile, having an S-score of -10.6. CONCLUSION: Conclusions: These findings suggest that the produced 6-aminocoumarin derivatives, specifically compound IIId, could serve as promising, effective inhibitors of carbonic anhydrase with potential anti-cancer activity targeting the carbonic anhydrase IX enzyme.