2. Academic Validation
  3. Design and synthesis of new 7-(N-substituted-methyl)-camptothecin derivatives as potent cytotoxic agents

Design and synthesis of new 7-(N-substituted-methyl)-camptothecin derivatives as potent cytotoxic agents

  • Bioorg Med Chem Lett. 2014 Aug 15;24(16):3850-3. doi: 10.1016/j.bmcl.2014.06.060.
Xiao-Bo Zhao 1,  Masuo Goto 2,  Zi-Long Song 1,  Susan L Morris-Natschke 2,  Yu Zhao 2,  Dan Wu 1,  Liu Yang 3,  Shu-Gang Li 1,  Ying-Qian Liu 4,  Gao-Xiang Zhu 1,  Xiao-Bing Wu 1,  Kuo-Hsiung Lee 5
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 Environmental and Municipal Engineering School, Lanzhou Jiaotong University, Lanzhou 730000, PR China.
  • 4 School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China. Electronic address: yqliu@lzu.edu.cn.
  • 5 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: 25008456 DOI: 10.1016/j.bmcl.2014.06.060
Abstract

A series of novel 7-(N-substituted-methyl)-camptothecin derivatives was designed, synthesized, and evaluated for in vitro cytotoxicity against four human tumor cell lines, A-549, MDA-MB-231, KB, and KBvin. All of the derivatives showed promising in vitro cytotoxic activity against the tested tumor cell lines, with IC50 values ranging from 0.0023 to 1.11 μM, and were as or more potent than topotecan. Compounds 9d, 9e, and 9r exhibited the highest antiproliferative activity among all prepared derivatives. Furthermore, all of the compounds were more potent than paclitaxel against the multidrug-resistant (MDR) KBvin subline. With a concise efficient synthesis and potent cytotoxic profiles, especially significant activity towards KBvin, compounds 9d, 9e, and 9r merit further development as a new generation of camptothecin-derived Anticancer clinical trial candidates.

Keywords

Antiproliferative activity; Camptothecin; Multidrug resistance.

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