Design, synthesis and potent cytotoxic activity of novel 7-(N-[(substituted-sulfonyl)piperazinyl]-methyl)-camptothecin derivatives. Issue 8 (15th April 2017)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 8(2017)
• Page Start: 1750
• Page End: 1753
• Publication Date: 2017-04-15
• Subjects: Camptothecin -- Cytotoxic activity -- Sulfonylpiperazine -- Synthesis; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.02.066
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: 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 μM to nM level, most of the new analogues showed greater cytotoxicity activity than the reference compounds irinotecan and topotecan. Furthermore, compounds12l (IC50, 1.2 nM) and12k (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.