Synthesis and characterization of novel dioxoacridine sulfonamide derivatives as new carbonic anhydrase inhibitors

Abstract

Novel dioxoacridine sulfonamide compounds were synthesized from reaction of cyclic 1,3-diketones, sulfanilamide (4-amino benzene sulfonamide) and aromatic aldehydes. The structures of these compounds were confirmed by using spectral analysis (IR, H-NMR, ¹³C-NMR, and mass). Human carbonic anhydrase isoenzymes (hCA I and hCA II) were purified from erythrocyte cells by affinity chromatography. The inhibitory effects of sulfanilamide, acetazolamide (AAZ), and newly synthesized sulfonamides on hydratase and esterase activities of these isoenzymes have been studied in vitro. The IC₅₀ values of compounds for esterase activity are 0.71–0.11 µM for hCA I and 0.45–0.12 µM for hCA II, respectively. The K_i values of these inhibitors were determined as 0,38–0,008 µM for hCA I and 0,19–0,001 µM for hCA II, respectively.

Keywords::

• Dioxoacridine sulfonamide
• carbonic anhydrase
• inhibition
• hydratase activity
• esterase activity

Acknowledgments

The authors are grateful to Prof. Dr. Yılmaz Yıldırır, Gazi University, Ankara, Turkey.

Declaration of interest

The authors are very grateful to Dumlupinar University Research Fund for providing financial support for this project (Grant No. 2008-4).