A Novel Class of Bis- and Tris-Chelate Diam(m)inebis(dicarboxylato)platinum(IV)Complexes as Potential Anticancer Prodrugs.

A novelclass of platinum(IV) complexes of the type [Pt(Am)(R(COO)2)2], where Am is a chelating diamine or two monodentateam(m)ine ligands and R(COO)2is a chelating dicarboxylatomoiety, was synthesized. For this purpose, the reaction between thecorresponding tetrahydroxidoplatinum(IV) precursors and variousdicarboxylic acids, such as oxalic, malonic, 3-methylmalonic, andcyclobutanedicarboxylic acid, was utilized. All new compounds werecharacterized in detail, using 1D and 2D NMR techniques, ESI-MS, FTIRspectroscopy, elemental analysis, TGA, and X-ray diffraction. Theirin vitro cytotoxicity was determined in a panel of human tumor celllines (CH1, SW480 and A549) by means of the MTT colorimetric assay.Furthermore, the lipophilicity and redox properties of the novel complexeswere evaluated in order to better understand their pharmacologicalbehavior. The most promising drug candidate, 4b(Pt(DACH)(mal)2), demonstrated low in vivo toxicity but profound anticanceractivity against both the L1210 leukemia and CT-26 colon carcinomamodels. [ABSTRACT FROM AUTHOR]