title: Synthesis and cytotoxic activity of dextran carrying cis-dichloro(cyclohexane-trans-l-1,2-diamine)platinum(II) complex.
abstract: cis-Dichloro(cyclohexane-trans-l-1,2-diamine)platinum(II) (Dach-Pt(chlorato)), is a platinum complex which is expected to exhibit higher antitumor activity than, and show no cross resistance with, cisplatin. However, its strong side-effects and low water-solubility have also been cited. We report that polymer/antitumor drug conjugates shows reduced side-effects and high antitumor activity. In order to provide a macromolecular prodrug of Dach-Pt having reduced side-effects and high water-solubility, we synthesized polymer conjugates of Dach-Pt and dextran derivatives having carboxylic acid groups, oxidized-dextran (OX-Dex)/Dach-Pt conjugate, and carboxymethyl-dextran(CM-Dex)/Dach-Pt conjugate. The cytotoxic activities of the conjugates were investigated against p388D1 lymphocytic leukemia cells in vitro. The OX-Dex/Dach-Pt conjugate showed almost the same level of cytotoxic activity as free Dach-Pt(chlorato). Although the cytotoxic activity of free Dach-Pt(chlorato) was decreased by incubation in medium with serum, the OX-Dex/Dach-Pt conjugate kept its cytotoxic activity in higher level after 24 h incubation in medium with serum. These results suggested that the stability of Dach-Pt molecule in the medium was increased and cytotoxic activity of Dach-Pt was not decreased by fixing to OX-Dex.
authors.affiliation: Department of Applied Chemistry, Faculty of Engineering, Kansai University, Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ohya
authors.forename: T
authors.initials: T
authors.lastname: Masunaga
authors.forename: T
authors.initials: T
authors.lastname: Baba
authors.forename: T
authors.initials: T
authors.lastname: Ouchi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D003692:Delayed-Action Preparations; D003911:Dextrans / Q000737:chemistry / Q000378:metabolism*; D016503:Drug Delivery Systems; D015195:Drug Design; D007945:Leukemia, Lymphoid / Q000473:pathology; D008970:Molecular Weight; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology; D010084:Oxidation-Reduction; D010984:Platinum / Q000378:metabolism; D011355:Prodrugs; D012995:Solubility; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D003911:Dextrans; D009944:Organoplatinum Compounds; D011355:Prodrugs; D010984:Platinum; C013933:dichloro-1,2-diaminocyclohexane platinum complex