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

摘要

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 a-CA isozymes purified from human and bovine (hCA I, hCA li, bCA III, hCA IV) tissues. The four isozymes showed quite diverse inhibition profiles with these compounds.The flavonoids inhibited hCA I with K,-s in the range of 2.2-12.8 uM, hCA II with K-s in the range of 0.74-6.2 uM, bCA III with K-s in the range of 2.2-21.3 uM, 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.