Design and synthesis of novel 7-[(N-substituted-thioureidopiperazinyl)-methyl]-camptothecin derivatives as potential cytotoxic agents. Issue 14 (17th July 2020)

• Record Type: Journal Article
• Authors: 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; Lee, Kuo-Hsiung
• Is Part Of: Natural product research. Volume 34:Issue 14(2020)
• Page Start: 2022
• Page End: 2029
• Publication Date: 2020-07-17
• Subjects: Camptothecin -- piperazinyl-thiourea -- cytotoxic activity -- synthesis; Natural products -- Periodicals; Natural products -- Research -- Periodicals; Biological Factors -- Periodicals; Biological Products -- Periodicals; 547
• DOI: 10.1080/14786419.2019.1573231
• Languages: English
• ISSNs: 1478-6419

Abstract

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: