Synthesis of Thiazole-methylsulfonyl Derivatives, X-ray Study, and Investigation of Their Carbonic Anhydrase Activities: <i>In Vitro</i> and <i>In Silico</i> Potentials

This study focused on the design, synthesis, chemical characterization, and potential inhibitory study of thiazole-methylsulfonyl derivatives against carbonic anhydrase enzymes. The synthesized compounds, with the characteristics of both the thiazole ring and methyl sulfonyl group, were synthesized through a two-step scheme, and their structures were confirmed through NMR spectroscopy and HRMS. Additionally, the structure of compound <b>2b</b> was elucidated by an X-ray study. An enzyme inhibition assay was performed to assess their biological activity against carbonic anhydrases, and the compounds showed promising results against carbonic anhydrases I and II, highlighting their potential for specificity and targeted therapy. The effects of these molecules on <i>in vitro</i> enzyme activities were investigated by spectrophotometric methods. For this purpose, the concentrations (IC₅₀ values) of compounds that inhibited the biological activities of carbonic anhydrase isoenzymes (hCA I and hCA II) by 50% were calculated. The IC₅₀ values were found between 39.38-198.04 μM (AAZ IC₅₀ = 18.11 μM) for hCA I and 39.16-86.64 μM (AAZ IC₅₀ = 20.65 μM). Molecular docking studies have shown that compounds <b>2a</b> and <b>2h</b> exhibit stable interaction networks with targeted enzymes. The combinations of both studies, enzyme inhibition assay and molecular docking studies, thus enlighten the significance of these compounds for further optimization for pharmacological profiling and for developing therapeutic agents against carbonic anhydrase. Moreover, the study provides insight for future research on the synthesis of heterocyclic compounds against carbonic anhydrase for therapeutic applications.