title: Synthesis, antitumor activity, and nephrotoxicity of the optical isomers of 2-aminomethylpyrrolidine(1,1-cyclobutane-dicarboxylato)platinum(II).
abstract: The optical isomers of 2-aminomethylpyrrolidine(1,1-cyclobutane- dicarboxylato)platinum(II) (DWA2114, 1), which has potent antitumor activity against various tumors, were synthesized. They were examined for antitumor activity against Colon 26 carcinoma in a sc-iv system, and changes in urinary protein and sugar levels in drug-treated mice were used as an index of nephrotoxicity. In their effect on tumors, (+)-(S)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +)platinum(II) (6b) was more potent than the enantiomer 6a in that the effective dose of 6b was smaller than that of 6a; but, both drugs exhibited potent antitumor activity. On the other hand, a distinct difference between 6a and 6b was shown in their nephrotoxicity. Isomer 6b induced a great increase in urinary protein and sugar levels in mice, whereas 6a caused no increase in these levels.
authors.affiliation: Exploratory Research Laboratories, Chugai Pharmaceutical Company Ltd., Gotemba-shi, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Morikawa
authors.forename: M
authors.initials: M
authors.lastname: Honda
authors.forename: K
authors.initials: K
authors.lastname: Endoh
authors.forename: T
authors.initials: T
authors.lastname: Matsumoto
authors.forename: K
authors.initials: K
authors.lastname: Akamatsu
authors.forename: H
authors.initials: H
authors.lastname: Mitsui
authors.forename: M
authors.initials: M
authors.lastname: Koizumi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D016190:Carboplatin / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D003110:Colonic Neoplasms / Q000188:drug therapy; D007668:Kidney / Q000187:drug effects*; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D013237:Stereoisomerism
chemical_list: D000970:Antineoplastic Agents; C058816:DWA 2114; D016190:Carboplatin