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

作　　者：HUANG HuoQiang1, 2, PAN XuLin1, JI ChangJiu1, 2, ZENG GuangZhi1, JIANG LiHua1, FU Xiang1, LIU JiKai1, HAO XiaoJiang1, ZHANG YingJun1 & TAN NingHua1 1 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, China 2 Graduate University of the Chinese Academy of Sciences, Beijing 100049, China 

出　　处：《Science China Chemistry》2009年第3期332-337,共6页中国科学（化学英文版）

基　　金：Supported by the National Natural Science Foundation of China (Grant No. 30725048);the Foundation of Chinese Academy of Sciences (West Light Program)

摘　　要：Carbonic anhydrase Ⅱ (CAⅡ) 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 CAⅡ, 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 in-hibitory activities against CAⅡ 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 soft-ware. Results indicated that the aliphatic chain and polar groups of hydroxyl and carboxyl are impor-tant to their inhibitory activities, providing a new insight into study on CA Ⅱ potent inhibitors.Carbonic anhydrase Ⅱ (CAⅡ) 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 CAⅡ, 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 in-hibitory activities against CAⅡ 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 soft-ware. Results indicated that the aliphatic chain and polar groups of hydroxyl and carboxyl are impor-tant to their inhibitory activities, providing a new insight into study on CA Ⅱ potent inhibitors.

关 键 词：carbonic anhydraseⅡ NATURAL INHIBITORS SCREENING DOCKING 

分 类 号：Q55[生物学—生物化学]