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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.BM

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.

Authors+Show Affiliations

School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China.Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, United States.School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China.Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, United States.Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, United States.School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China.Environmental and Municipal Engineering School, Lanzhou Jiaotong University, Lanzhou 730000, PR China.School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China.School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China. Electronic address: yqliu@lzu.edu.cn.School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China.School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China.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.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25008456

Citation

Zhao, Xiao-Bo, et al. "Design and Synthesis of New 7-(N-substituted-methyl)-camptothecin Derivatives as Potent Cytotoxic Agents." Bioorganic & Medicinal Chemistry Letters, vol. 24, no. 16, 2014, pp. 3850-3.
Zhao XB, Goto M, Song ZL, et al. Design and synthesis of new 7-(N-substituted-methyl)-camptothecin derivatives as potent cytotoxic agents. Bioorg Med Chem Lett. 2014;24(16):3850-3.
Zhao, X. B., Goto, M., Song, Z. L., Morris-Natschke, S. L., Zhao, Y., Wu, D., Yang, L., Li, S. G., Liu, Y. Q., Zhu, G. X., Wu, X. B., & Lee, K. H. (2014). Design and synthesis of new 7-(N-substituted-methyl)-camptothecin derivatives as potent cytotoxic agents. Bioorganic & Medicinal Chemistry Letters, 24(16), 3850-3. https://doi.org/10.1016/j.bmcl.2014.06.060
Zhao XB, et al. 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. PubMed PMID: 25008456.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Design and synthesis of new 7-(N-substituted-methyl)-camptothecin derivatives as potent cytotoxic agents. AU - Zhao,Xiao-Bo, AU - Goto,Masuo, AU - Song,Zi-Long, AU - Morris-Natschke,Susan L, AU - Zhao,Yu, AU - Wu,Dan, AU - Yang,Liu, AU - Li,Shu-Gang, AU - Liu,Ying-Qian, AU - Zhu,Gao-Xiang, AU - Wu,Xiao-Bing, AU - Lee,Kuo-Hsiung, Y1 - 2014/06/27/ PY - 2014/05/09/received PY - 2014/06/17/revised PY - 2014/06/19/accepted PY - 2014/7/11/entrez PY - 2014/7/11/pubmed PY - 2015/3/7/medline KW - Antiproliferative activity KW - Camptothecin KW - Multidrug resistance SP - 3850 EP - 3 JF - Bioorganic & medicinal chemistry letters JO - Bioorg. Med. Chem. Lett. VL - 24 IS - 16 N2 - 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. SN - 1464-3405 UR - https://www.unboundmedicine.com/medline/citation/25008456/Design_and_synthesis_of_new_7__N_substituted_methyl__camptothecin_derivatives_as_potent_cytotoxic_agents_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0960-894X(14)00688-X DB - PRIME DP - Unbound Medicine ER -