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

A novel class of platinum(IV) complexes of the type [Pt(Am)(R(COO)2)2], where Am is a chelating diamine or two monodentate
am(m)ine ligands and R(COO)2 is a chelating dicarboxylato
moiety, was synthesized. For this purpose, the reaction between the
corresponding tetrahydroxidoplati­num(IV) precursors and various
dicarboxylic acids, such as oxalic, malonic, 3-methylmalonic, and
cyclobutanedicarboxylic acid, was utilized. All new compounds were
characterized in detail, using 1D and 2D NMR techniques, ESI-MS, FTIR
spectroscopy, elemental analysis, TGA, and X-ray diffraction. Their
in vitro cytotoxicity was determined in a panel of human tumor cell
lines (CH1, SW480 and A549) by means of the MTT colorimetric assay.
Furthermore, the lipophilicity and redox properties of the novel complexes
were evaluated in order to better understand their pharmacological
behavior. The most promising drug candidate, 4b (Pt(DACH)(mal)2), demonstrated low in vivo toxicity but profound anticancer
activity against both the L1210 leukemia and CT-26 colon carcinoma
models.