title: Camptothecin: current perspectives.
abstract: This review provides a detailed discussion of recent advances in the medicinal chemistry of camptothecin, a potent antitumor antibiotic. Two camptothecin analogues are presently approved for use in the clinic as antitumor agents and several others are in clinical trials. Camptothecin possesses a novel mechanism of action involving the inhibition of DNA relaxation by DNA topoisomerase I, and more specifically the stabilization of a covalent binary complex formed between topoisomerase I and DNA. This review summarizes the current status of studies of the mechanism of action of camptothecin, including topoisomerase I inhibition and additional cellular responses. Modern synthetic approaches to camptothecin and several of the semi-synthetic methods are also discussed. Finally, a systematic evaluation of novel and important analogues of camptothecin and their contribution to the current structure-activity profile are considered.
authors.affiliation: Departments of Chemistry and Biology, University of Virginia, Charlottesville, VA 22901, USA.
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Thomas
authors.forename: Nicolas J
authors.initials: NJ
authors.lastname: Rahier
authors.forename: Sidney M
authors.initials: SM
authors.lastname: Hecht
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors
chemical_list: D000970:Antineoplastic Agents; D059004:Topoisomerase I Inhibitors; D004247:DNA; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin