Synthesis of New Acetazolamide Analogues Bearing Thiazole Moiety with Promising Carbonic Anhydrase Inhibitory Activity

Abstract

Objective: Breast cancer is remarkably predominant among female malignancies. Numerous targets exist for breast cancer therapy; carbonic anhydrase enzyme is one such target due to its crucial function in the tumor microenvironment. Aim: Design four new compounds based on the core scaffolds of acetazolamide and thiazole. Methodology: The synthesis process of these compounds involves four steps including: acidic amide hydrolysis, N-chloroacetylation, thiazole ring cyclization, and finally Schiff base reaction. The structures of the final products were confirmed using proton nuclear magnetic resonance spectroscopy. Furthermore, their cytotoxic activities were evaluated. Results: In vitro MTT cytotoxic assays against MCF-7 (breast cancer) and MCF-10A (normal breast) cell lines, demonstrating encouraging anticancer potential, and promising selective compounds. Conclusion: Each of the designed compounds was successfully synthesized and demonstrated both potent anticancer activity and high selectivity.