The new trans-Pt complexes, derived from trans-[PtCl2(amine)(dimethylamine)] and trans-[PtCl2(OH)2(amine)(dimethylamine)], were synthesized and characterized studying the structure-activity relationship and testing their antiproliferative activity. Their evaluation as cytotoxic agents towards different cancer and normal cell lines is presented. These compounds are active in a panel of tumor cell lines at low micromolar range. Compounds seems to be more active in tumoral than in normal primary human cell lines. Cytotoxic activity is closely related to the amine ligand. Cyclohexylamine ligand was the most active among the amine-ligands tested. Cytotoxic activity correlates with an increase in annexin V positive cells indicating an apoptotic effect of the compounds. Mechanistically, the antitumor activity correlates with a blockade of the cell cycle in S phase and a complete abolishment of G2/M checkpoint arrest suggesting physical interaction of compound with DNA inhibiting S phase transition.