溴代二苯甲酮及其衍生物的合成与碳酸酐酶同工酶抑制作用
Synthesis and carbonic anhydrase isoenzymes inhibitory effects of brominated diphenylmethanone and its derivatives.
作者信息
Çetinkaya Yasin, Göçer Hülya, Gülçin Ilhami, Menzek Abdullah
机构信息
Faculty of Science, Department of Chemistry, Atatürk University, Erzurum, Turkey; Department of Food Technology, Oltu Vocational School, Atatürk University, Oltu-Erzurum, Turkey.
出版信息
Arch Pharm (Weinheim). 2014 May;347(5):354-9. doi: 10.1002/ardp.201300349. Epub 2014 Mar 6.
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 µM, Ki = 2.19 µM) whereas compound 5 was found to be the best inhibitor for isoenzyme hCA II (IC50 = 1.33 µM, Ki = 2.09 µM). Probably, stable conformations of 5 and 10 are more convenient for interaction with CA isoenzymes than those of the other compounds.
合成了包括CO、Br和OH（苄基和酚羟基）在内的已知和新型衍生物，以及(3,4-二甲氧基苯基)(2,3,4-二甲氧基苯基)甲酮的相应苄醇，并研究了它们对碳酸酐酶（CA）同工酶I和II的抑制作用。碳酸酐酶是催化二氧化碳（CO₂）可逆水合生成碳酸氢根（HCO₃⁻）的金属酶。测试了二苯甲酮衍生物5-18对人碳酸酐酶（hCA，EC 4.2.1.1）同工酶（hCA I和hCA II）的抑制作用，它们在微摩尔水平上抑制了这两种同工酶。发现化合物5和10是针对两种CA同工酶的最佳抑制剂。根据我们的数据，化合物10是同工酶hCA I的最佳抑制剂（IC50 = 3.48 μM，Ki = 2.19 μM），而化合物5被发现是同工酶hCA II的最佳抑制剂（IC50 = 1.33 μM，Ki = 2.09 μM）。可能，化合物5和10的稳定构象比其他化合物的构象更便于与CA同工酶相互作用。
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