Mou Ke, Xu Bo, Ma Chao, Yang Xiaoming, Zou Xiaomin, Lü Yang, Xu Ping
Department of Medicinal Chemistry, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100083, PR China.
Bioorg Med Chem Lett. 2008 Mar 15;18(6):2198-202. doi: 10.1016/j.bmcl.2007.12.077. Epub 2008 Feb 2.
A series of peptidyl vinyl ester derivatives bearing three different P1 substitutions as potential proteasome inhibitors were studied. The target molecules were designed based on CADD (computer aided drug design) protocol and synthesized. Their activities toward proteasome and four human cancer cell lines (including hepatoma cell line (Bel-7402), myeloid leukemic cell line (HL-60), gastric cancer cell line (BGC-823) and nasopharyngeal cancer cell line (KB)) were tested using fluorescence assay. Two compounds showed proteasome inhibitory activities, and four compounds showed weak antiproliferative activities toward HL-60 and BGC-823.
研究了一系列带有三种不同P1取代基作为潜在蛋白酶体抑制剂的肽基乙烯基酯衍生物。基于计算机辅助药物设计（CADD）方案设计并合成了目标分子。使用荧光测定法测试了它们对蛋白酶体和四种人类癌细胞系（包括肝癌细胞系（Bel-7402）、髓性白血病细胞系（HL-60）、胃癌细胞系（BGC-823）和鼻咽癌细胞系（KB））的活性。两种化合物表现出蛋白酶体抑制活性，四种化合物对HL-60和BGC-823表现出较弱的抗增殖活性。
