2. Academic Validation
  3. Design and synthesis of novel spin-labeled camptothecin derivatives as potent cytotoxic agents

Design and synthesis of novel spin-labeled camptothecin derivatives as potent cytotoxic agents

  • Bioorg Med Chem. 2014 Nov 15;22(22):6453-8. doi: 10.1016/j.bmc.2014.09.035.
Xiao-Bo Zhao 1,  Dan Wu 1,  Mei-Juan Wang 1,  Masuo Goto 2,  Susan L Morris-Natschke 2,  Ying-Qian Liu 3,  Xiao-Bing Wu 1,  Zi-Long Song 1,  Gao-Xiang Zhu 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: 25438769 DOI: 10.1016/j.bmc.2014.09.035
Abstract

In our continuing search for natural product-based spin-labeled antitumor drugs, 20 novel spin-labeled camptothecin derivatives were synthesized via a Cu-catalyzed one pot reaction and evaluated for cytotoxicity against four human tumor cell lines (A-549, MDA-MB-231, KB, and KBvin). Eighteen of the target compounds (9a, 9b, 9d-9k, 9m-9t) exhibited significant in vitro antiproliferative activity against these four tested tumor cell lines. Compounds 9e and 9j (IC50 0.057 and 0.072μM, respectively) displayed the greatest cytotoxicity against the multidrug-resistant (MDR) KBvin cell line and merit further development into preclinical and clinical drug candidates for treating Cancer including MDR phenotype.

Keywords

C-20 position; Camptothecin; Cytotoxic activity; Spin-labeled.

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