Design and synthesis of novel 7-[(N-substituted-thioureidopiperazinyl)-methyl]-camptothecin derivatives as potential cytotoxic agents.
Autor: 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
Publication year: 2020
Natural product research
issn:1478-6427 1478-6419
doi: 10.1080/14786419.2019.1573231
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 (IC(50) = 0.275 μM) possessed similar or better antiproliferative activity against the multidrug-resistant (MDR) KBvin subline than that of topotecan (IC(50) = 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.
Language: eng
Rights:
Pmid: 30784310
Tags: Humans; Cell Line, Tumor; Structure-Activity Relationship; Cell Proliferation/drug effects; Drug Screening Assays, Antitumor; *Drug Design; cytotoxic activity; Camptothecin/*analogs & derivatives/chemical synthesis/pharmacology; Antineoplastic Agents/*chemical synthesis/pharmacology; Camptothecin; Cytotoxins/*chemical synthesis/pharmacology; piperazinyl-thiourea; synthesis
Link: https://pubmed.ncbi.nlm.nih.gov/30784310/
