Design and synthesis of novel 7-[(N-substituted-thioureidopiperazinyl)-methyl]-camptothecin derivatives as potential cytotoxic agents
Design and synthesis of novel 7-[(N-substituted-thioureidopiperazinyl)-methyl]-camptothecin derivatives as potential cytotoxic agents
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DOI：
10.1080/14786419.2019.1573231
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发表时间：
2019-02
影响因子：
2.2
通讯作者：
Zilong Song;Guan-Zhou Yang;Jun-Cai Li;Ying-Qian Liu;Cheng‐Jie Yang;M. Goto;Zhi-Jun Zhang;S. Morris-Nat
中科院分区：
文献类型：
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作者：
Zilong Song;Guan-Zhou Yang;Jun-Cai Li;Ying-Qian Liu;Cheng‐Jie Yang;M. Goto;Zhi-Jun Zhang;S. Morris-Nat
本论文设计、合成了16个具有哌嗪硫脲化学骨架和不同取代基的喜树碱（CPT）衍生物，并对5种肿瘤细胞株（A-549、MDA-MB-231、MCF-7、KB和KBvin）进行了体外细胞毒活性研究。结果，所有合成的化合物对测试的五种肿瘤细胞系显示出有希望的体外细胞毒活性，并且比伊立替康更有效。重要的是，化合物13 g（IC 50 = 0.514 μM）和13 o（IC 50 = 0.275 μM）具有与拓扑替康（IC 50 = 0.511 μM）相似或更好的抗多药耐药（MDR）KBvin亚系的抗增殖活性，值得进一步开发作为临床试验的抗癌候选物。有了这些结果，我们有理由得出结论，将哌嗪基硫脲基序到喜树碱的位置-7赋予良好的细胞毒活性对癌细胞系，可能导致新的抗癌药物。图形摘要
Abstract As part of continuing our research on diverse C-7 derivatives of camptothecin (CPT), 16 CPT derivatives bearing piperazinyl-thiourea chemical scaffold and different substituent groups have been designed, synthesized and evaluated in vitro for cytotoxicity against five tumor cell lines (A-549, MDA-MB-231, MCF-7, KB and KBvin). As a result, all the synthesized compounds showed promising in vitro cytotoxic activity against the five tumor cell lines tested, and were more potent than irinotecan. Importantly, compounds 13 g (IC50 = 0.514 μM) and 13o (IC50 = 0.275 μM) possessed similar or better antiproliferative activity against the multidrug-resistant (MDR) KBvin subline than that of topotecan (IC50 = 0.511 μM) and merit further development as anticancer candidates for clinical trail. With these results in hand, we have a reason to conclude that incorporating piperazinyl-thiourea motifs into position-7 of camptothecin confers well cytotoxic activity against cancer cell lines, probably resulting in new anticancer drugs. Graphical Abstract