Ruthenium (II)/allopurinol complex inhibits breast cancer progression via multiple targets

Ingrid O Travassos, Francyelli Mello-Andrade, Raíssa P Caldeira, Wanessa C Pires, Paula F F da Silva, Rodrigo S Correa, Tamara Teixeira, Alisson Martins-Oliveira, Alzir A Batista, Elisângela P de Silveira-Lacerda
Journal of Biological Inorganic Chemistry: JBIC 2021 April 10
Metal complexes based on ruthenium have established excellent activity with less toxicity and great selectivity for tumor cells. This study aims to assess the anticancer potential of ruthenium(II)/allopurinol complexes called [RuCl2 (allo)2 (PPh3 )2 ] (1) and [RuCl2 (allo)2 (dppb)] (2), where allo means allopurinol, PPh3 is triphenylphosphine and dppb, 1,4-bis(diphenylphosphino)butane. The complexes were synthesized and characterized by elemental analysis, IR, UV-Vis and NMR spectroscopies, cyclic voltammetry, molar conductance measurements, as well as the X-ray crystallographic analysis of complex 2. The antitumor effects of compounds were determined by cytotoxic activity and cellular and molecular responses to cell death mechanisms. Complex 2 showed good antitumor profile prospects because in addition to its cytotoxicity, it causes cell cycle arrest, induction of DNA damage, morphological and biochemical alterations in the cells. Moreover, complex 2 induces cell death by p53-mediated apoptosis, caspase activation, increased Beclin-1 levels and decreased ROS levels. Therefore, complex 2 can be considered a suitable compound in antitumor treatment due to its cytotoxic mechanism.

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