Mutagenic Tests Confirm That New Acetylacetonate Pt(II) Complexes Induce Apoptosis in Cancer Cells Interacting with Nongenomic Biological Targets

New platinum(II) complexes [PtCl( O,O′ -acac)(L)] ( 1 ) and [Pt( O,O′ -acac)( γ -acac)(L)] ( 2 ) (L = DMSO, a ; DMS, b ) containing a single chelated ( O,O′ -acac) ( 1 ), or one chelated and one σ -bonded ( γ -acac) acetylacetonate ( 2 ) have been synthesized. The new Pt(II) complexes exhibited high in vitro cytotoxicity on cisplatin sensitive and resistant cell lines and showed negligible reactivity with nucleobases (Guo and 5′-GMP) but selective substitution of DMSO/DMS with soft biological nucleophiles, such as L-methionine. In order to assess the ability of the new complexes with respect to cisplatin to induce apoptosis by interaction with nongenomic targets, the Ames' test, a standard reverse mutation assay, was carried out on two Salmonella typhimurium strains (TA98 and TA100). Interestingly, the new complexes did not show the well-known mutagenic activity exhibited by cisplatin and are, therefore, able to activate apoptotic pathways without interacting with DNA.