title: Synthesis and antitumor activity of 20(S)-camptothecin derivatives. A-ring-substituted 7-ethylcamptothecins and their E-ring-modified water-soluble derivatives.
abstract: Twenty-six novel A-ring-modified 7-ethylcamptothecins (6) were synthesized by Friedländer's condensation of the chiral tricyclic ketone (5) with aminopropiophenones (4). The compounds substituted with fluorine at the 11 position showed strong cytotoxicity to KB and L1210 cells. The 11-fluoro derivatives also exhibited strong inhibitory activity on DNA topoisomerase I. Nine compounds 6 with four to ten times stronger cytotoxicity than that of camptothecin were selected and converted into water-soluble 17-O-acyl amide derivatives (8). Compounds 8e (10-Me, O-COCH2CH2SCH3) and 8f (11-F, O-COC2H5) showed activity towards Meth A in mice that was comparable to that of CPT-11, at lower doses than CPT-11.
authors.affiliation: Yakult Central Institute for Microbiological Research, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yaegashi
authors.forename: S
authors.initials: S
authors.lastname: Sawada
authors.forename: H
authors.initials: H
authors.lastname: Nagata
authors.forename: T
authors.initials: T
authors.lastname: Furuta
authors.forename: T
authors.initials: T
authors.lastname: Yokokura
authors.forename: T
authors.initials: T
authors.lastname: Miyasaka
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007624:KB Cells; D007939:Leukemia L1210 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D010946:Plants, Medicinal / Q000737:chemistry; D059004:Topoisomerase I Inhibitors
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D059004:Topoisomerase I Inhibitors; D002166:Camptothecin