title: Design and synthesis of novel PEG-conjugated 20(S)-camptothecin sulfonylamidine derivatives with potent in vitro antitumor activity via Cu-catalyzed three-component reaction.
abstract: In our continuing search for camptothecin (CPT)-derived antitumor drugs, novel structurally diverse PEG-based 20(S)-CPT sulfonylamidine derivatives were designed, synthesized via a Cu-multicomponent reaction (MCR), and evaluated for 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, and were more potent than irinotecan. Significantly, these derivatives exhibited comparable cytotoxicity against KBvin, while irinotecan was less active against this cell line. With a concise efficient synthesis and potent cytotoxic profiles, especially significant activity towards KBvin, these compounds merit further development as a new generation of CPT-derived PEG-conjugated drug candidates.
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China.
authors.forename: Zi-Long
authors.initials: ZL
authors.lastname: Song
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China.
authors.forename: Hai-Le
authors.initials: HL
authors.lastname: Chen
authors.affiliation: School of Medicine, Shandong University, Jinan 250012, PR China.
authors.forename: Yu-Han
authors.initials: YH
authors.lastname: Wang
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: Wen-Jing
authors.initials: WJ
authors.lastname: Gao
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China.
authors.forename: Pi-Le
authors.initials: PL
authors.lastname: Cheng
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: 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: Mei-Juan
authors.initials: MJ
authors.lastname: Wang
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 / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002384:Catalysis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003300:Copper; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D000077146:Irinotecan; D007624:KB Cells; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D011092:Polyethylene Glycols; C115093:pegamotecan; D000077146:Irinotecan; D003300:Copper; D002166:Camptothecin
keywords: C-20 position; Camptothecin; Cytotoxic activity; Poly(ethylene glycol) (PEG); Sulfonylamidine