Syntheses and antiproliferative activities of rebeccamycin analogues bearing two 7-azaindole moieties
Syntheses and antiproliferative activities of rebeccamycin analogues bearing two 7-azaindole moieties
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DOI：
10.1016/s0968-0896(02)00532-1
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发表时间：
2003-03-06
影响因子：
3.5
通讯作者：
Prudhomme, M
中科院分区：
文献类型：
--
作者：
Marminon, C;Pierré, A;Prudhomme, M
作为雷贝卡霉素类似物构效关系研究的一部分，合成了含有两个氮杂吲哚基团的化合物，在酰亚胺氮上既有甲基又有氢原子。阿扎因多尔亚基有望通过与靶酶(S)更强的氢键来增强对肿瘤细胞的细胞毒作用。测定了化合物8、10和19对一组肿瘤细胞的细胞毒作用，并与瑞贝霉素、去氯瑞贝霉素2和N-甲基化类似物A进行了比较，同时评价了它们对L1210细胞周期的影响。具有酰亚胺NH功能的化合物19对L1210细胞的细胞毒作用最强，在细胞周期的G2+M期诱导细胞聚集最多。与它们的非氮杂类似物对所有受试细胞株具有细胞毒性不同，二氮杂化合物10和19对某些细胞系表现出选择性。(C)2002爱思唯尔科学有限公司。保留所有权利。
As a part of structure activity relationship studies on rebeccamycin analogues, compounds containing two aza-indole moieties were synthesized bearing either a methyl group or a hydrogen atom on the imide nitrogen. The azaindole substructures were expected to enhance the cytotoxicity toward tumor cell lines through stronger hydrogen bonding with the target enzyme(s). The cytotoxicities of compounds 8, 10 and 19 against a panel of tumor cell lines were examined and compared with those of rebeccamycin, dechlorinated rebeccamycin 2 and N-methylated analogue A. Their effect on the L1210 cell cycle was also evaluated. Compound 19, having an imide NH function had the strongest cytotoxicity towards L1210 cells and induced the largest accumulation of cells in the G2 + M phases of the cell cycle. In contrast to their non-aza analogues, which were cytotoxic for all the cell lines tested, diaza compounds 10 and 19 showed selectivity for some cell lines. (C) 2002 Elsevier Science Ltd. All rights reserved.