Synthesis and antitumor activity evaluation of a novel series of camptothecin analogs
Synthesis and antitumor activity evaluation of a novel series of camptothecin analogs
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一系列新型喜树碱类似物的合成及抗肿瘤活性评价
DOI：
10.1080/10286020.2013.804068
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发表时间：
2013-08-01
影响因子：
1.7
通讯作者：
Yu, Peng
中科院分区：
文献类型：
--
作者：
Lv, Jian;Guo, Na;Yu, Peng
合成了一系列新的10位取代喜树碱类似物（3-10），并对其生物活性进行了评价。喜树碱型天然产物的氨基酸连接的氨基甲酸酯衍生物（8-10）不仅对三种人肿瘤细胞系K562、HepG 2和HT-29具有良好至优异的抑制活性，而且对正常人细胞HEK 293显示出显著较小的细胞毒性（半数最大抑制浓度> 10 M）。相对于正常细胞，化合物9对肿瘤细胞的选择性比喜树碱好至少250倍。初步实验结果表明，这些化合物的溶解度也比10-羟基喜树碱有所提高。
A series of novel 10-substituted camptothecin analogs (3-10) with a carbamate linker were synthesized, and their biological activities were evaluated. The amino acid-linked carbamate derivatives (8-10) of the camptothecin-type natural product not only possessed good to excellent inhibitory activity against three human tumor cell lines K562, HepG2, and HT-29, but also showed significantly less cytotoxicity against normal human cell HEK293 (half maximal inhibiting concentration >10M). The selectivity of compound 9 toward tumor cells relative to normal cells is at least 250 times better than that of camptothecin. The preliminary testing result indicated that the solubility of these compounds was also improved compared to that of 10-hydroxy camptothecin.