Carbonic anhydrase inhibitors: in vitro inhibition of α isoforms (hCA I, hCA II, bCA III, hCA IV) by flavonoids

Abstract

A series of flavonoids, such as quercetin, catechin, apigenin, luteolin, morin, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase (CA). The compounds were tested against four α-CA isozymes purified from human and bovine (hCA I, hCA II, bCA III, hCA IV) tissues. The four isozymes showed quite diverse inhibition profiles with these compounds. The flavonoids inhibited hCA I with K_I-s in the range of 2.2–12.8 μM, hCA II with K_I-s in the range of 0.74–6.2 μM, bCA III with K_I-s in the range of 2.2–21.3 μM, and hCA IV with inhibition constants in the range of 4.4–15.7, with an esterase assay using 4-nitrophenyl acetate as substrate. Some simple phenols/sulfonamides were also investigated as standard inhibitors. The flavonoids incorporate phenol moieties which inhibit these CAs through a diverse, not yet determined inhibition mechanism, compared to classic inhibitors such as the sulfonamide/sulfamate ones.

Keywords::

• Carbonic anhydrase
• flavonoid
• inhibitor
• phenol

Declarations of interest

This study was financed by Turkish Republic Prime Ministry State Planning Organization (DPT), (Project no: 2010K120440) for (MS) and by an FP7 EU grant (Metoxia) to CTS. The authors report no declarations of interest.