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

Abstract

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.