Three-component synthesis and carbonic anhydrase inhibitory properties of novel octahydroacridines incorporating sulfaguanidine scaffold

摘要

Abstract Novel sulfaguanidines incorporating acridine moiety were synthesized by the reaction of cyclohexane-1,3-dione, sulfaguanidine, and aromatic aldehydes. Synthesis of these compounds was performed in water at room temperature, and their structures were confirmed by using spectral analysis (IR, 1H-NMR, 13C-NMR, and HRMS). Human carbonic anhydrase isoenzymes (hCA I and II) were purified from erythrocyte cells with affinity chromatography. hCA I was purified 83.40-fold with a specific activity, 1060.9 EU mg protein?1, and hCA II was purified 262.32-fold with a specific activity, 3336.8 EU mg protein?1. The inhibitory effects of newly synthesized sulfaguanidines and acetazolamide, (AAZ) as a control compound, on hydratase and esterase activities of these isoenzymes have been studied in vitro. Synthesized compounds have moderate inhibition potentials on hCA I and hCA II isoenzymes. IC₅₀ values of compounds for esterase activity are in the range of 118.4?±?7.0?μM–257.5?±?5.2?μM for hCA I and 86.7?±?3.0?μM–249.4?±?10.2?μM for hCA II, respectively.