Dual Antitumor and Antiangiogenic Activity of Organoplatinum(II) Complexes

A library of over 20 cycloplatinated compounds of the type [Pt­(dmba-R)­LCl] (dmba-R = C,N-dimethylbenzylamine-like ligand; R being MeO, Me, H, Br, F, CF₃, and NO₂ substituents in the R₅ or R₄ position of the phenyl ring; L = DMSO and P­(C₆H₄CF₃-p)₃) has been prepared. All compounds are active in both human ovarian carcinoma A2780 cells and cisplatin-resistant A2780cisR cells, with most of the DMSO platinum complexes exhibiting IC₅₀ values in the submicromolar range in the A2780 cell line. Interestingly, DMSO platinum complexes show low cytotoxicity in the nontumorigenic kidney cell line BGM and therefore high selectivity factors SF. In addition, some of the DMSO platinum complexes effectively inhibit angiogenesis in the human umbilical vein endothelial cell line EA.hy926. These are the first platinum­(II) complexes reported to inhibit angiogenesis at a close concentration to their IC₅₀ in A2780 cells, turning them into dual cytotoxic and antiangiogenic compounds.