Some phenolic natural compounds as carbonic anhydrase inhibitors: An in vitro and in silico study

This paper presents experimental and molecular docking studies on the inhibitory effects of tyrosol, hydroxytyrosol, luteolin, diosmetin, caffeic acid, luteolin 7-O-glycoside, and apigenin 7-O-glycoside from olive (Olea europaea L.) leaf against human carbonic anhydrase (hCA, E.C.4.2.1.1) isozymes I and II. After these isozymes were separately purified, their activities were determined using the esterase activity. IC₅₀ values for hCA I and II were calculated as 2.02-11.38 µM and 2.23-9.05 µM, respectively. The compounds were identified as CA inhibitors, with K_i values in the ranges of 1.66-9.17 µM for the hCA I isozyme and 1.49-14.21 µM for hCA II. The inhibitory effects of these natural compounds were also compared to acetazolamide, which is a potent inhibitor of both CA isozymes. Our results may contribute to the synthesis of new CA inhibitors and pave the way for new drug design in the treatment of a number of diseases including cancer, obesity, diabetes, and glaucoma.