Design, synthesis, and cytotoxic activity of novel 7-substituted camptothecin derivatives incorporating piperazinyl-sulfonylamidine moieties. Issue 17 (1st September 2017)

• Record Type: Journal Article
• Authors: Yang, Cheng-Jie; Song, Zi-Long; Goto, Masuo; Liu, Ying-Qian; Hsieh, Kan-Yen; Morris-Natschke, Susan L.; Zhao, Yong-Long; Zhang, Jun-Xiang; Lee, Kuo-Hsiung
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 17(2017)
• Page Start: 3959
• Page End: 3962
• Publication Date: 2017-09-01
• Subjects: CKD-602 belotecan -- CPT camptothecin -- CPT-11 irinotecan -- DMF dimethylformamide -- MDR multi-drug resistant -- SAR structure-activity relationship -- TFA trifluoroacetic acid -- topo topoisomerase -- TPT topotecan; Camptothecin -- Cytotoxic activity -- Piperazine -- Sulfonylamidine -- Synthesis; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.07.078
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: In our continuing search for camptothecin (CPT)-derived antitumor drugs, novel 7-substituted CPT derivatives incorporating piperazinyl-sulfonylamidine moieties were designed, synthesized and evaluated for cytotoxicity against five tumor cell lines (A-549, MDA-MB-231, MCF-7, KB, and KB-VIN). All of the derivatives showed promising in vitro cytotoxic activity against the tested tumor cell lines, and were more potent than irinotecan. Remarkably, most of the compounds exhibited comparable cytotoxicity against the multidrug-resistant (MDR) KB-VIN and parental KB tumor cell lines, while irinotecan lost activity completely against KB-VIN. Especially, compounds13r and13p (IC50 0.38 and 0.85 μM, respectively) displayed the greatest cytotoxicity against the MDR KB-VIN cell line and merit further development into preclinical and clinical drug candidates for treating cancer, including MDR phenotype.