Naphthazarin derivatives (IV): synthesis, inhibition of DNA topoisomerase I and cytotoxicity of 2-or 6-acyl-5,8-dimethoxy-1,4-naphahoquinones
Naphthazarin derivatives (IV): synthesis, inhibition of DNA topoisomerase I and cytotoxicity of 2-or 6-acyl-5,8-dimethoxy-1,4-naphahoquinones
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DOI：
10.1016/s0223-5234(00)00129-x
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发表时间：
2000-03-01
影响因子：
6.7
通讯作者：
Ahn, BZ
中科院分区：
文献类型：
--
作者：
Song, GY;Kim, Y;Ahn, BZ
合成了一些 2- 或 6-酰基-5,8-二甲氧基-1, 1-萘醌 (DMNQ) 衍生物，并评估了其对 DNA 拓扑异构酶 I 的抑制作用以及对 L1210 细胞的细胞毒性。与2-酰基-DMNQ衍生物相比，6-酰基-DMNQ化合物具有更高的亲电醌部分，在抑制DNA拓扑异构酶I和细胞毒性方面表现出更高的效力，这意味着亲电芳基化可能参与其生物活性。酶抑制的时间和温度依赖性表明芳基化发生不可逆。在 6-酰基-DMNQ 衍生物中，具有中等大小酰基 (C-5-C-9) 的衍生物比其他衍生物显示出更高的生物活性。此外，为了有效抑制DNA拓扑异构酶I，6-酰化衍生物的酰基部分的大小似乎限于<12个碳原子。 (C) 2000 年科学与医学 Elsevier SAS 版。
Some 2- or 6-acyl-5,8-dimethoxy-1, 1-naphthoquinone (DMNQ) derivatives were synthesized and evaluated for inhibition of DNA topoisomerase I and cytotoxicity against L1210 cells. Compared with 2-acyl-DMNQ derivatives, 6-acyl-DMNQ compounds, bearing a higher electrophilic quinone moiety, showed a higher potency in the inhibition of DNA topoisomerase I and the cytotoxicity, implying the possible participation of electrophilic arylation in their bioactivities. Time and temperature dependence of the enzyme inhibition suggests that the arylation occurs irreversibly. Among the 6-acyl-DMNQ derivatives, the ones possessing an acyl group of an intermediate size (C-5-C-9) showed higher potency in their bioactivities than other derivatives. Furthermore, for the effective inhibition of DNA topoisomerase I, the size of acyl moiety of 6-acylated derivatives seems to be limited to < 12 carbon atoms. (C) 2000 Editions scientifiques er medicales Elsevier SAS.