title: Synthesis and biological activity of some bile acid-based camptothecin analogues.
abstract: In an effort to decrease the toxicity of camptothecin (CPT) and improve selectivity for hepatoma and colon cancer cells, bile acid groups were introduced into the CPT 20 or 10 positions, resulting in the preparation of sixteen novel CPT-bile acid analogues. The compounds in which a bile acid group was introduced at the 20-hydroxyl group of CPT showed better cytotoxic selectivity for human hepatoma and colon cancer cells than for human breast cancer cells. Fluorescence microscopy analysis demonstrated that one compound (E2) entered human hepatoma cells more effectively than it did human breast cancer cells. Compound G4 exhibited the best anti-tumour activity in vivo. These results suggested that introduction of a bile acid group at the 20-position of CPT could decrease toxicity in vivo and improve selectivity for hepatoma cells.
authors.affiliation: College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China. lixingnuo@zjut.edu.cn.
authors.forename: Xingnuo
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Forest Plant Ecology (Northeast Forestry University), Ministry of Education, 332# No. 26 Hexing Road, Harbin 150040, China. li_qingyong@163.com.
authors.forename: Tengfei
authors.initials: T
authors.lastname: Zhao
authors.affiliation: College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China. Chengdp@zjut.edu.cn.
authors.forename: Dongping
authors.initials: D
authors.lastname: Cheng
authors.affiliation: College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China. chuchu@zjut.edu.cn.
authors.forename: Chu
authors.initials: C
authors.lastname: Chu
authors.affiliation: College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China. sqtong@zjut.edu.cn.
authors.forename: Shengqiang
authors.initials: S
authors.lastname: Tong
authors.affiliation: College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China. yjz@zjut.edu.cn.
authors.forename: Jizong
authors.initials: J
authors.lastname: Yan
authors.affiliation: College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China. liqy@zjut.edu.cn.
authors.forename: Qing-Yong
authors.initials: QY
authors.lastname: Li
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000494:pharmacology; D001647:Bile Acids and Salts / Q000737:chemistry* / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004355:Drug Stability; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001647:Bile Acids and Salts; D002166:Camptothecin