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

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.

Keywords:

• Acridine
• carbonic anhydrase
• inhibition
• sulfaguanidine

Declaration of interest

The authors are very grateful to Dumlupınar University Research Fund for providing financial support for this project (Grant No. 2011-16 and Grant No. 2012-38).

Supplementary material available online