表霉素类似物作为DNA聚合酶抑制剂的构效关系
Structure-activity relationships of epolactaene analogs as DNA polymerases inhibitors.
作者信息
Kuramochi Kouji, Mizushina Yoshiyuki, Nagata Seigo, Sugawara Fumio, Sakaguchi Kengo, Kobayashi Susumu
机构信息
Frontier Research Center for Genome and Drug Discovery, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
出版信息
Bioorg Med Chem. 2004 May 1;12(9):1983-9. doi: 10.1016/j.bmc.2004.03.007.
Epolactaene, a neuritogenic compound in human neuroblastoma cells, showed inhibitory activities against DNA polymerases alpha and beta. The synthesis and inhibitory activities of epolactaene analogs are described. The alpha,beta-epoxy-gamma-lactam moiety in the core and the length of the side chain greatly influenced the activities. Compound 5 was the strongest inhibitor of DNA polymerase alpha and beta of all synthesized compounds with IC(50) values of 13 and 78 microM, respectively. N- and O-alkyl derivatives that had modified core moieties showed moderate inhibition.
依泊拉烯是一种存在于人类神经母细胞瘤细胞中的促神经突生长化合物，对DNA聚合酶α和β具有抑制活性。本文描述了依泊拉烯类似物的合成及其抑制活性。核心结构中的α,β-环氧-γ-内酰胺部分和侧链长度对活性有很大影响。化合物5是所有合成化合物中对DNA聚合酶α和β最强的抑制剂，其IC(50)值分别为13和78微摩尔。具有修饰核心部分的N-和O-烷基衍生物表现出中等程度的抑制作用。
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