title: Synthesis and antitumor activity of novel 20s-camptothecin analogues.
abstract: In an effort to decrease the toxicity and improve the stability of labile lactone ring of camptothecin, nitrogenous heterocyclic aromatic groups were introduced into 20-position of camptothecin and seventeen new 20s-camptothecin derivatives were obtained in quantitative yield. The cytotoxicity in vitro on three cancer cell lines and the stability of the lactone in phosphate-buffered solution (PBS) of these derivatives were evaluated. Most of these tested derivatives possessed better cytotoxicity than topotecan. Analogues 6, 12 exhibited the best antitumor activity in vivo in all derivatives we prepared. The results suggested that introduction of pyrazole in 10- or 20-position of camptothecin could promote antitumor activity in vitro and in vivo, simultaneously bring much increase of the stability of lactone.
authors.affiliation: Key Laboratory of Forest Plant Ecology, Northeast Forestry University, Ministry of Education, No. 26 Hexing Road, Harbin 150040, China. li_qingyong@163.com
authors.forename: Qingyong
authors.initials: Q
authors.lastname: Li
authors.forename: Hongyan
authors.initials: H
authors.lastname: Lv
authors.forename: Yuangang
authors.initials: Y
authors.lastname: Zu
authors.forename: Zhenhuan
authors.initials: Z
authors.lastname: Qu
authors.forename: Liping
authors.initials: L
authors.lastname: Yao
authors.forename: Lin
authors.initials: L
authors.lastname: Su
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.forename: Limin
authors.initials: L
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans
chemical_list: D000970:Antineoplastic Agents; D002166:Camptothecin