【摘 要】
：
Metronidazole-sulfonamide derivatives 4a-4l,a new class of human carbonic anhydrase inhibitors(hCA),were designed,synthesized,isolated,and evaluated for their ability to inhibit the enzymatic activity
【机 构】
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State Key Laboratory of Pharmaceutical Biotechnology,Nanjing University,Nanjing 210093,China
【出 处】
：
第八届国际分子模拟与信息技术应用学术会议
论文部分内容阅读
Metronidazole-sulfonamide derivatives 4a-4l,a new class of human carbonic anhydrase inhibitors(hCA),were designed,synthesized,isolated,and evaluated for their ability to inhibit the enzymatic activity of the physiologically dominant isozymes hCA Ⅱ and the tumor-associated isozyme hCA Ⅸ(h = human).Many of these compounds inhibited CA Ⅱ and Ⅸ in the range of 16-137 and 38-169 nM,respectively.Among all the compounds,the most potent inhibitor against hCA Ⅱ and Ⅸ were compounds 4b(IC50 = 16 nM)and 4h(IC50-38 nM).Conversely compounds 4e and 4d displayed the most potent growth inhibitory activity against B16-F10 and MCF-7 cancer cell lines in vitro,respectively,with an IC50 value of 150 nM for B16-F10 and 6.5 nM for MCF-7.These metronidazole-sulfonamide derivatives may prove interesting lead candidates to target tumor-associated CA isozymes,wherein the CA domain is located extracellularly.All the new compounds were evaluated for cytotoxicity against human macrophages by MTT assay.
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