title: 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.
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Prov. le Lecce/Monteroni, 73100 Lecce, Italy.
authors.forename: Sandra Angelica
authors.initials: SA
authors.lastname: De Pascali
authors.forename: Federica
authors.initials: F
authors.lastname: Lugoli
authors.forename: Antonella
authors.initials: A
authors.lastname: De Donno
authors.forename: Francesco Paolo
authors.initials: FP
authors.lastname: Fanizzi