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

A novel class of tetrakis(carboxylato)platinum(IV) complexes, [Pt(O2CR)(4)( dach)] = (dach = trans(+/-)-1, 2-diaminocyclohexane; R = CnH2n+1, n = 1 sim ilar to 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 carboxyla te 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 similar to -403 mV) depending on the chain length of the carboxylate ligand was relatively sma ll. Among the title complexes, the tetrakis(propionato)platinum(IV) complex , [Pt(O2CC2H5)(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 nud e mice.