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

Abstract

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 mu M and 2.23-9.05 mu M, respectively. The compounds were identified as CA inhibitors, with K-i values in the ranges of 1.66-9.17 mu M for the hCA I isozyme and 1.49-14.21 mu M 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.