title: Synthesis and Biological Evaluation of Novel Water-Soluble Poly-(ethylene glycol)-10-hydroxycamptothecin Conjugates.
abstract: In order to improve the antitumor activity and water solubility of 10-hydroxycamptothecin (HCPT), a series of novel HCPT conjugates were designed and synthesized by conjugating polyethylene glycol (PEG) to the 10-hydroxyl group of HCPT via a valine spacer. The in vitro stability of these synthesized compounds was determined in pH 7.4 buffer at 37 °C, and the results showed that they released HCPT at different rates. All the compounds demonstrated significant antitumor activity in vitro against K562, HepG2 and HT-29 cells. Among them, compounds, 4a, 4d, 4e and 4f, exhibited 2-5 times higher potency than HCPT. The stability and antitumor activity of these conjugates were found to be closely related to the length of PEG and the linker type, conjugates with a relatively short PEG chain and carbamate linkages (compounds 4a and 4f) exhibited controlled release of HCPT and excellent antitumor in vitro activity.
authors.affiliation: Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science and Technology, No.29, 13th Avenue, TEDA, Tianjin 300457, China. guona@tust.edu.cn.
authors.forename: Na
authors.initials: N
authors.lastname: Guo
authors.affiliation: Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science and Technology, No.29, 13th Avenue, TEDA, Tianjin 300457, China. jiangduwill@126.com.
authors.forename: Du
authors.initials: D
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science and Technology, No.29, 13th Avenue, TEDA, Tianjin 300457, China. wangluyao_1106@163.com.
authors.forename: Luyao
authors.initials: L
authors.lastname: Wang
authors.affiliation: Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science and Technology, No.29, 13th Avenue, TEDA, Tianjin 300457, China. youxing_2013@126.com.
authors.forename: Xing
authors.initials: X
authors.lastname: You
authors.affiliation: Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science and Technology, No.29, 13th Avenue, TEDA, Tianjin 300457, China. tyo201485@tust.edu.cn.
authors.forename: Yu-Ou
authors.initials: YO
authors.lastname: Teng
authors.affiliation: Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science and Technology, No.29, 13th Avenue, TEDA, Tianjin 300457, China. yupeng@tust.edu.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Yu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019073:HT29 Cells; D056945:Hep G2 Cells; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000494:pharmacology*; D012995:Solubility
chemical_list: D000970:Antineoplastic Agents; D011092:Polyethylene Glycols; C028098:10-hydroxycamptothecin; D002166:Camptothecin
keywords: PEG; antitumor; conjugate; hydroxycamptothecin