6‐(1‐Acyloxyalkyl)‐5,8‐dimethoxy‐1,4‐naphthoquinone (DMNQ; 5,8‐dimethoxy‐1,4‐naphthoquinone) derivatives were synthesized and examined for their inhibitory effect on DNA topoisomerase‐I (Topo I) and their antiproliferative activity against L1210 cells. The Topo‐I inhibitory effect of 6‐(1‐hydroxyalkyl)‐DMNQ derivatives was found to be dependent on the size of the alkyl chains, suggesting that lipophilicity might be one important factor influencing the inhibitory effect. It was found that acylation of 6‐(1‐hydroxyalkyl)‐ DMNQ derivatives possessing alkyl chains of C2‐C5 enhanced both bioactivities, suggesting that an increase of electrophilicity in the quinoid moiety makes the electrophilic arylation of bionucleophiles more favorable. It is noteworthy that 6‐(1‐heptanoyloxyethyl)‐ DMNQ exhibited both the most potent Topo I inhibitory activity (IC50, 11.5 μM) and the greatest antiproliferative activity (ED50, 0.05 μM) upon L1210 cells.

中文翻译：

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Naphthazarin 衍生物 (VIII)：6-(1-酰氧基烷基)-5,8-二甲氧基-1,4-萘醌的合成、对 DNA 拓扑异构酶-I 的抑制作用和抗增殖活性

合成了 6-(1-酰氧基烷基)-5,8-二甲氧基-1,4-萘醌 (DMNQ; 5,8-二甲氧基-1,4-萘醌) 衍生物并检查了它们对 DNA 拓扑异构酶-I (Topo I) 及其对 L1210 细胞的抗增殖活性。发现 6-(1-羟烷基)-DMNQ 衍生物的 Topo-I 抑制作用取决于烷基链的大小，表明亲脂性可能是影响抑制作用的一个重要因素。发现具有C2-C5烷基链的6-(1-羟烷基)-DMNQ衍生物的酰化增强了两种生物活性，表明醌型部分亲电性的增加使生物亲核试剂的亲电芳基化更加有利。值得注意的是，6-(1-庚酰氧基乙基)-DMNQ 表现出最有效的 Topo I 抑制活性 (IC50,