Carbonic anhydrase inhibitors: Synthesis, molecular docking, cytotoxic and inhibition of the human carbonic anhydrase isoforms I, II, IX, XII with novel benzenesulfonamides incorporating pyrrole, pyrrolopyrimidine and fused pyrrolopyrimidine moieties
Carbonic anhydrase inhibitors: Synthesis, molecular docking, cytotoxic and inhibition of the human carbonic anhydrase isoforms I, II, IX, XII with novel benzenesulfonamides incorporating pyrrole, pyrrolopyrimidine and fused pyrrolopyrimidine moieties
复制标题
DOI：
10.1016/j.bmc.2014.05.009
复制
发表时间：
2014-07-15
影响因子：
3.5
通讯作者：
Supuran, Claudiu T.
中科院分区：
文献类型：
--
作者：
Ghorab, Mostafa M.;Alsaid, Mansour S.;Supuran, Claudiu T.
以吡咯邻氨基腈为关键中间体，合成了一系列具有生物活性的苯磺酰胺基吡咯、吡咯并嘧啶、吡唑并吡咯并嘧啶、三唑并吡咯并嘧啶、四唑并吡咯并嘧啶、三嗪并吡咯并嘧啶和吡咯并嘧啶并三氮杂卓类化合物。评价所有合成的化合物对人（h）同种型hCA I、II、IX和XII的体外碳酸酐酶（CA，EC4.2.1.1）抑制作用。在测试的衍生物中，化合物16、18和20-24显示出作为肿瘤相关跨膜同种型（hCA IX和XII）的抑制剂的有效活性，在纳摩尔和亚纳摩尔范围内，具有高选择性。所有化合物在人乳腺癌细胞系（MCF-7）上进行细胞毒活性测定，显示出与临床使用的药物阿霉素相当的有效活性。(C)2014爱思唯尔有限公司版权所有。
A series of novel pyrroles, pyrrolopyrimidines, pyrazolopyrrolopyrimidine, triazolopyrrolopyrimidines, tetrazolopyrrolopyrimidine, triazinopyrrolopyrimidines and pyrrolopyrimidotriazepines bearing the biologically active benzenesulfonamide moiety were synthesized by using pyrrole-o-amino-carbonitrile as key intermediate. All the synthesized compounds were evaluated for their in vitro carbonic anhydrase (CA, EC 4.2.1.1) inhibitory effects against the human (h) isoforms hCA I, II, IX and XII. Among the tested derivatives, compounds 16, 18 and 20-24 showed potent activity as inhibitors for the tumor associated transmembrane isoforms (hCA IX and XII) in the nanomolar and subnanomolar range, with high selectivity. All compounds underwent cytotoxic activity assays on human breast cancer cell line (MCF-7) showing effective activity, comparable to that of the clinically used drug doxorubicin. (C) 2014 Elsevier Ltd. All rights reserved.