Carbonic anhydrase inhibitors: guaiacol and catechol derivatives effectively inhibit certain human carbonic anhydrase isoenzymes (hCA I, II, IX and XII)

Abstract

Carbonic anhydrases (CAs) are widespread metalloenzymes in higher vertebrates including humans. A series of phenolic compounds, including guaiacol, 4-methylguaiacol, 4-propylguaiacol, eugenol, isoeugenol, vanillin, syringaldehyde, catechol, 3-methyl catechol, 4-methyl catechol and 3-methoxy catechol were investigated for their inhibition of all the catalytically active mammalian isozymes of the Zn²⁺-containing CA (EC 4.2.1.1). All the phenolic compounds effectively inhibited human carbonic anhydrase isoenzymes (hCA I, II, IX and XII), with K_is in the range of 2.20–515.98 μM. The various isozymes showed diverse inhibition profiles. Among the tested phenolic derivatives, compounds 4-methyl catechol and 3-methoxy catechol showed potent activity as inhibitors of the tumour-associated transmembrane isoforms (hCA IX and XII) in the submicromolar range, with high selectivity. The results obtained from this research may lead to the design of more effective carbonic anhydrase isoenzyme inhibitors (CAIs) based on such phenolic compound scaffolds.

• Carbonic anhydrases
• catechol derivatives
• enzyme inhibition
• guaiacol derivatives
• isoenzymes

Declaration of interest

The authors declared that there is no conflict of interest. This work was financed in part by two EU projects of the 7th FP, Metoxia and Dynano.

IG would like to extend their sincere appreciation to the Deanship of Scientific Research at King Saud University for its funding of this research through the Research Group Project no RGP-VPP-254.