Hautefaye Patrick, Cimetière Bernard, Pierré Alain, Léonce Stéphane, Hickman John, Laine William, Bailly Christian, Lavielle Gilbert
Institut de Recherches Servier, 125 Chemin de Ronde, 78290, Croissy sur Seine, France.
Bioorg Med Chem Lett. 2003 Aug 18;13(16):2731-5. doi: 10.1016/s0960-894x(03)00534-1.
Ten novel camptothecin (CPT) derivatives devoid of the lactone function in the E-ring were synthesized and evaluated as anticancer agents. Several of these CPT analogues bearing a five-membered E-ring are potent inhibitors of the DNA relaxation and cleavage reactions catalyzed by topoisomerase I and exhibit promising cytotoxic activities with IC(50) values in the nM range. This is the first successful design of lactone-free CPT, providing thus a new avenue to the development of topoisomerase I targeted antitumor agents.
合成了10种在E环中没有内酯功能的新型喜树碱（CPT）衍生物，并将其作为抗癌剂进行评估。这些带有五元E环的CPT类似物中有几种是拓扑异构酶I催化的DNA松弛和切割反应的有效抑制剂，并表现出有前景的细胞毒性活性，其半数抑制浓度（IC50）值在纳摩尔范围内。这是无内酯CPT的首次成功设计，从而为开发靶向拓扑异构酶I的抗肿瘤药物提供了一条新途径。
