title: Design and synthesis of new 7-(N-substituted-methyl)-camptothecin derivatives as potent cytotoxic agents.
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.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China.
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Zhao
authors.affiliation: Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, United States.
authors.forename: Masuo
authors.initials: M
authors.lastname: Goto
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China.
authors.forename: Zi-Long
authors.initials: ZL
authors.lastname: Song
authors.affiliation: Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, United States.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Morris-Natschke
authors.affiliation: Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, United States.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wu
authors.affiliation: Environmental and Municipal Engineering School, Lanzhou Jiaotong University, Lanzhou 730000, PR China.
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China.
authors.forename: Shu-Gang
authors.initials: SG
authors.lastname: Li
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China. Electronic address: yqliu@lzu.edu.cn.
authors.forename: Ying-Qian
authors.initials: YQ
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China.
authors.forename: Gao-Xiang
authors.initials: GX
authors.lastname: Zhu
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China.
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002166:Camptothecin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007624:KB Cells; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002166:Camptothecin
keywords: Antiproliferative activity; Camptothecin; Multidrug resistance