Design, synthesis and potent cytotoxic activity of novel 7-(N-[(substituted-sulfonyl)piperazinyl]-methyl)-camptothecin derivatives

作者：Zhu, Gao-Xiang; Cheng, Pi-Le; Goto, Masuo; Zhang, Na; Morris-Natschke, Susan L.; Hsieh, Kan-Yen; Yang, Guan-Zhou; Yang, Qian-Ru; Liu, Ying-Qian^*; Chen, Hai-Le; Zhang, Xiao-Shuai; Lee, Kuo-Hsiung^*

来源：Bioorganic & Medicinal Chemistry Letters, 2017, 27(8): 1750-1753.

DOI：10.1016/j.bmcl.2017.02.066

• Camptothecin
• Cytotoxic activity
• Sulfonylpiperazine
• Synthesis

In an effort to discover potent camptothecin-derived antitumor agents, novel camptothecin analogues with sulfonylpiperazinyl motifs at position-7 were designed and synthesized. They were evaluated for in vitro cytotoxicity with the sulforhodamine-B (SRB) method in five types of human tumor cell lines, A-549, MDA-MB-231, KB, KB-VIN and MCF-7. With IC50 values in the low mu M to nM level, most of the new analogues showed greater cytotoxicity activity than the reference compounds irinotecan and topotecan. Furthermore, compounds 121 (IC50, 1.2 nM) and 12k (IC50, 20.2 nM) displayed the highest cytotoxicity against the multidrug-resistant (MDR) KB-VIN cell line and merit further development as preclinical drug candidates for treating cancer, including MDR phenotype. Our study suggested that integration of sulfonylpiperazinyl motifs into position-7 of camptothecin is an effective strategy for discovering new potent cytotoxic camptothecin derivatives.

• 出版日期2017-4-15
• 单位中国医科大学; 兰州大学