Synthesis and oral antitumor activity of tetrakis(carboxylato)platinum(IV) complexes.

摘要: 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 oral antitumor activity. Lipophilicity aqueous solubility the title complexes were greatly dependent on alkyl chain length carboxylate ligand, their partition coefficient changed by 4 or 5 orders magnitude from acetate to hexanoate complexes. On other hand, range cathodic reduction potential (-546 -403 mV) depending ligand relatively small. Among tetrakis(propionato)platinum(IV) complex, [Pt(O(2)CC(2)H(5))(4)(dach)], with appropriate lipophilicity (log P 0.18) (14.6 mg/mL) found exhibit better activity than JM216 against human ovarian tumor xenograft SKOV3 in nude mice.