title: Synthesis and antitumor activities of amino acid prodrugs of amino-combretastatins.
abstract: The synthesis and antitumor activity of water-soluble amino acid prodrugs of amino-combretastatins were reported. Among the synthesized compounds, 7e (CS-39-L-Ser HCI, AC-7700) showed enhanced antitumor activity and decreased toxicity in a Colon 26 murine adenocarcinoma model. Compound 7e showed improved solubility and was easily formulated for in vivo administration. Compound 7e was cleaved to generate the parent compound, CS-39, in the whole blood of mice as well as man, possibly by the action of amino peptidase on the erythrocyte membrane.
authors.affiliation: Pharmaceutical Research Laboratories, Ajinomoto Co Inc., Kawasaki, Japan. koji_ohsumi@ajinomoto.com
authors.forename: K
authors.initials: K
authors.lastname: Ohsumi
authors.forename: T
authors.initials: T
authors.lastname: Hatanaka
authors.forename: R
authors.initials: R
authors.lastname: Nakagawa
authors.forename: Y
authors.initials: Y
authors.lastname: Fukuda
authors.forename: Y
authors.initials: Y
authors.lastname: Morinaga
authors.forename: Y
authors.initials: Y
authors.lastname: Suga
authors.forename: Y
authors.initials: Y
authors.lastname: Nihei
authors.forename: K
authors.initials: K
authors.lastname: Ohishi
authors.forename: Y
authors.initials: Y
authors.lastname: Akiyama
authors.forename: T
authors.initials: T
authors.lastname: Tsuji
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D001632:Bibenzyls / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000188:drug therapy; D015195:Drug Design; D004355:Drug Stability; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D011355:Prodrugs / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D012995:Solubility; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D001632:Bibenzyls; D011355:Prodrugs