Synthesis and Carbonic Anhydrase Isoenzymes Inhibitory Effects of Brominated Diphenylmethanone and Its Derivatives

被引：72

作者：

Cetinkaya, Yasin ^{[1
,2
]}

Gocer, Hulya ^{[3
]}

Gulcin, Ilhami ^{[1
]}

Menzek, Abdullah ^{[1
]}

机构：

[1] Ataturk Univ, Fac Sci, Dept Chem, TR-25240 Erzurum, Turkey

[2] Ataturk Univ, Dept Food Technol, Oltu Vocat Sch, Oltu Erzurum, Turkey

[3] Ibrahim Cecen Univ Agri, Cent Researching Lab, Agri, Turkey

来源：

ARCHIV DER PHARMAZIE | 2014年 / 347卷 / 05期

关键词：

Benzylalcohol; Bromination; Carbonic anhydrase; Enzyme inhibition; Reduction; ERYTHROCYTE ISOZYMES I; BROMOPHENOL DERIVATIVES; ANTIOXIDANT PROPERTIES; PHENOLIC-COMPOUNDS; ENZYME-ACTIVITY; ISOFORMS I; VITRO; VIVO; PURIFICATION; ACTIVATORS;

D O I：

10.1002/ardp.201300349

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Known and novel derivatives including CO, Br, and OH (benzylic and phenolic), and the corresponding benzylic alcohols of (3,4-dimethoxyphenyl)(2,3,4-dimethoxyphenyl)methanone were synthesized, and their inhibitory effects on the carbonic anhydrase (CA) isoenzymes I and II were investigated. CAs are the metalloenzymes catalyzing the reversible hydration of carbon dioxide (CO2) to bicarbonate (HCO3-). The inhibitory effects of diphenylmethanone derivatives 5-18 were tested on human CA (hCA, EC 4.2.1.1) isoenzymes (hCA I and hCA II) and they inhibited both isoenzymes at micromolar levels. Compounds 5 and 10 were found to be the best inhibitors against both CA isoenzymes. According to our data, compound 10 was the best inhibitor for isoenzyme hCA I (IC50=3.48 mu M, K-i=2.19 mu M) whereas compound 5 was found to be the best inhibitor for isoenzyme hCA II (IC50=1.33 mu M, K-i=2.09 mu M). Probably, stable conformations of 5 and 10 are more convenient for interaction with CA isoenzymes than those of the other compounds.

引用

页码：354 / 359

页数：6

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