Synthesis and evaluation of thiazolyl coumarin drug conjugates as carbonic anhydrase isozyme inhibitors by using integrated invitro and insilico approaches.

A new series of thiazolyl-coumarin-drug conjugates were synthesized through the reaction of 3-bromoacetylcoumarin and N-substituted and N, N-di-substituted thioureas. The synthesized compounds were characterized by1H-NMR,13C-NMR and FTIR spectroscopy and thoroughly analyzed through in-vitro and in-silico studies. Among these, derivatives 8b and 8d demonstrated significant inhibitory effects during in vitro analysis. Compound 8b exhibited a notable inhibition potential exhibiting IC50 = 0.32 ± 0.04 µM against CAIX, while compound 8d showed a potent inhibitory effect with IC50 = 0.38 ± 0.02 µM and 0.61 ± 0.05 µM against CAII and CAXII isozymes, respectively. Surpassing its standard inhibitor acetazolamide. Electronic characteristics of all synthesized hybrid compounds were accessed via density functional theory calculations (DFTs). Furthermore, the results were validated via molecular docking studies. Drug likeness properties were predicted at the end via ADMET analysis, to support the investigations. The comprehensive experimental and computational analyses supported the conclusion that the synthesized hybrid compounds possess the potential to act as inhibitors against different types of carbonic anhydrases. Overall, this study will open new avenues for the development of dual inhibitors of CAII and CAXII, displaying versatile therapeutic applications.