1. Design and synthesis of novel 7-[(N-substituted-thioureidopiperazinyl)-methyl]-camptothecin derivatives as potential cytotoxic agents.
- Author
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Song, Zi-Long, Yang, Guan-Zhou, Li, Jun-Cai, Liu, Ying-Qian, Yang, Chen-Jie, Goto, Masuo, Zhang, Zhi-Jun, Morris-Natschke, Susan L., Liu, Hua, and Lee, Kuo-Hsiung
- Subjects
THIOUREA ,CAMPTOTHECIN ,CELL lines ,ANTINEOPLASTIC agents ,CANCER cells - 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 (IC
50 = 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. [ABSTRACT FROM AUTHOR]- Published
- 2020
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