title: Synthesis and antitumor activity of 7-ethyl-9-alkyl derivatives of camptothecin.
abstract: A series of new camptothecin derivatives, as topoisomerase I inhibitor, were synthesized to identify potent antitumor agents. The synthesis method was based on the Claisen rearrangement of 10-allyloxy-7-ethylcamptothecin. All of the compounds were assayed for cytotoxicity against two human tumor cell lines, Bel7402, HCT116, and showed good potency in vitro. Compounds 2, 4, 9, were assessed for the stability of lactone in human plasma. And then compound 2 was tested for antitumor activity in vitro against mouse tumor sarcoma-180. The results suggested that the small alkyl groups in the both 7- and 9-positions of camptothecin could promote liposolubility, antitumor activity in vitro and vivo, though did not bring much increase of the stability of lactone.
authors.affiliation: Shanghai Institute of Materia Medica, SIBS, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, 555 Zuchongzhi Road, Zhangjiang High-Tech Park, Shanghai 201203, China.
authors.forename: Heyong
authors.initials: H
authors.lastname: Gao
authors.forename: Xiongwen
authors.initials: X
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.forename: Hongwu
authors.initials: H
authors.lastname: Shen
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.forename: Jian
authors.initials: J
authors.lastname: Ding
authors.forename: Chuan
authors.initials: C
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D006801:Humans
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002166:Camptothecin