Screening and docking studies of natural phenolic inhibitors of carbonic anhydrase II

Carbonic anhydrase II (CA II) is an important enzyme complex with Zn²⁺, which is involved in many physiological and pathological processes, such as calcification, glaucoma and tumorigenicity. In order to search for novel inhibitors of CA II, inhibition assay of carbonic anhydrase II was performed, by which seven natural phenolic compounds, including four phenolics (grifolin, 4-O-methyl-grifolic acid, grifolic acid, and isovanillic acid) and three flavones (eriodictyol, quercetin and puerin A), showed inhibitory activities against CA II with IC₅₀s in the range of 6.37–71.73 μmol/L. Grifolic acid is the most active one with IC₅₀ of 6.37 _μmol/L. These seven phenolic compounds were proved to be novel natural carbonic anhydrase II inhibitors, which were obtained in flexible docking study with GOLD 3.0 software. Results indicated that the aliphatic chain and polar groups of hydroxyl and carboxyl are important to their inhibitory activities, providing a new insight into study on CA II potent inhibitors. Authors with the equal contribution Supported by the National Natural Science Foundation of China (Grant No. 30725048) and the Foundation of Chinese Academy of Sciences (West Light Program).