2. Academic Validation
  3. Design, synthesis, and cytotoxic activity of novel 7-substituted camptothecin derivatives incorporating piperazinyl-sulfonylamidine moieties

Design, synthesis, and cytotoxic activity of novel 7-substituted camptothecin derivatives incorporating piperazinyl-sulfonylamidine moieties

  • Bioorg Med Chem Lett. 2017 Sep 1;27(17):3959-3962. doi: 10.1016/j.bmcl.2017.07.078.
Cheng-Jie Yang 1,  Zi-Long Song 1,  Masuo Goto 2,  Ying-Qian Liu 3,  Kan-Yen Hsieh 2,  Susan L Morris-Natschke 2,  Yong-Long Zhao 1,  Jun-Xiang Zhang 1,  Kuo-Hsiung Lee 4
Affiliations

Affiliations

  • 1 School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China.
  • 2 Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, United States.
  • 3 School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China. Electronic address: yqliu@lzu.edu.cn.
  • 4 Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, United States; Chinese Medicine Research and Development Center, China Medical University and Hospital, Taichung, Taiwan. Electronic address: khlee@email.unc.edu.
PMID: 28789891 DOI: 10.1016/j.bmcl.2017.07.078
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, compounds 13r and 13p (IC50 0.38 and 0.85μM, 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.

Keywords

Camptothecin; Cytotoxic activity; Piperazine; Sulfonylamidine; Synthesis.

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