Novel Platinum(II) and Platinum(IV) Antitumor Agents that Exhibit Potent Cytotoxicity and Selectivity.

A novel platinum(II) complex and its platinum(IV) derivative were synthesized and characterized. Cytotoxicity studies against mesenchymal cells (MCs) and lung (A549), breast (MDA-MB-231), and melanoma (A375) cancer cells demonstrated 7-20-fold superior activity for both complexes relative to cisplatin. Remarkably, demonstrated 17-22-fold greater selectivity toward the cancerous cells compared to the non-cancerous MCs. Western blot analysis on A549 cells showed the involvement of the intrinsic apoptotic pathway. Cellular fractionation and uptake experiments in A549 cells using ICP-mass spectrometry (MS) indicated that and cross the cellular membrane predominantly via active transport mechanisms. The significant improvement in selectivity that is exhibited by is reported for the first time for this class of complexes.