title: Synthesis and oral antitumor activity of tetrakis(carboxylato)platinum(IV) complexes.
abstract: A novel class of tetrakis(carboxylato)platinum(IV) complexes, [Pt(O(2)CR)(4)(dach)] (dach = trans-(+/-)-1,2-diaminocyclohexane; R = C(n)H(2n+1), n = 1 approximately 5), was synthesized and studied for physicochemical properties and oral antitumor activity. Lipophilicity and aqueous solubility of the title complexes were greatly dependent on the alkyl chain length of the carboxylate ligand, and their partition coefficient and solubility changed by 4 or 5 orders of magnitude from acetate to hexanoate complexes. On the other hand, the range of their cathodic reduction potential (-546 approximately -403 mV) depending on the chain length of the carboxylate ligand was relatively small. Among the title complexes, the tetrakis(propionato)platinum(IV) complex, [Pt(O(2)CC(2)H(5))(4)(dach)], with appropriate lipophilicity (log P = 0.18) and aqueous solubility (14.6 mg/mL) was found to exhibit better oral antitumor activity than JM216 against the human ovarian tumor xenograft SKOV3 in nude mice.
authors.affiliation: Inorganic Chemistry Laboratory, Korea Institute of Science and Technology, Seoul 130-650, Korea.
authors.forename: Y A
authors.initials: YA
authors.lastname: Lee
authors.forename: S S
authors.initials: SS
authors.lastname: Lee
authors.forename: K M
authors.initials: KM
authors.lastname: Kim
authors.forename: C O
authors.initials: CO
authors.lastname: Lee
authors.forename: Y S
authors.initials: YS
authors.lastname: Sohn
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012995:Solubility; D013329:Structure-Activity Relationship; D014183:Transplantation, Heterologous
chemical_list: C461190:(1,2-diaminiocyclohexane)tetrakis(propionato)platinum(IV); D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds