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Design, synthesis, and cytotoxic activity of novel 7-substituted camptothecin derivatives incorporating piperazinyl-sulfonylamidine moieties.
Bioorg Med Chem Lett. 2017 09 01; 27(17):3959-3962.BM

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.

Authors+Show Affiliations

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.School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China. Electronic address: yqliu@lzu.edu.cn.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.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

Language

eng

PubMed ID

28789891

Citation

Yang, Cheng-Jie, et al. "Design, Synthesis, and Cytotoxic Activity of Novel 7-substituted Camptothecin Derivatives Incorporating Piperazinyl-sulfonylamidine Moieties." Bioorganic & Medicinal Chemistry Letters, vol. 27, no. 17, 2017, pp. 3959-3962.
Yang CJ, Song ZL, Goto M, et al. Design, synthesis, and cytotoxic activity of novel 7-substituted camptothecin derivatives incorporating piperazinyl-sulfonylamidine moieties. Bioorg Med Chem Lett. 2017;27(17):3959-3962.
Yang, C. J., Song, Z. L., Goto, M., Liu, Y. Q., Hsieh, K. Y., Morris-Natschke, S. L., Zhao, Y. L., Zhang, J. X., & Lee, K. H. (2017). Design, synthesis, and cytotoxic activity of novel 7-substituted camptothecin derivatives incorporating piperazinyl-sulfonylamidine moieties. Bioorganic & Medicinal Chemistry Letters, 27(17), 3959-3962. https://doi.org/10.1016/j.bmcl.2017.07.078
Yang CJ, et al. Design, Synthesis, and Cytotoxic Activity of Novel 7-substituted Camptothecin Derivatives Incorporating Piperazinyl-sulfonylamidine Moieties. Bioorg Med Chem Lett. 2017 09 1;27(17):3959-3962. PubMed PMID: 28789891.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Design, synthesis, and cytotoxic activity of novel 7-substituted camptothecin derivatives incorporating piperazinyl-sulfonylamidine moieties. AU - Yang,Cheng-Jie, AU - Song,Zi-Long, AU - Goto,Masuo, AU - Liu,Ying-Qian, AU - Hsieh,Kan-Yen, AU - Morris-Natschke,Susan L, AU - Zhao,Yong-Long, AU - Zhang,Jun-Xiang, AU - Lee,Kuo-Hsiung, Y1 - 2017/07/29/ PY - 2017/05/18/received PY - 2017/07/26/revised PY - 2017/07/28/accepted PY - 2017/8/10/pubmed PY - 2017/9/9/medline PY - 2017/8/10/entrez KW - Camptothecin KW - Cytotoxic activity KW - Piperazine KW - Sulfonylamidine KW - Synthesis SP - 3959 EP - 3962 JF - Bioorganic & medicinal chemistry letters JO - Bioorg. Med. Chem. Lett. VL - 27 IS - 17 N2 - 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. SN - 1464-3405 UR - https://www.unboundmedicine.com/medline/citation/28789891/Design_synthesis_and_cytotoxic_activity_of_novel_7_substituted_camptothecin_derivatives_incorporating_piperazinyl_sulfonylamidine_moieties_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0960-894X(17)30785-0 DB - PRIME DP - Unbound Medicine ER -