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J Biol Inorg Chem ; 26(4): 385-401, 2021 06.
Article in English | MEDLINE | ID: mdl-33837856

ABSTRACT

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.


Subject(s)
Allopurinol/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Mammary Neoplasms, Animal/drug therapy , Ruthenium Compounds/chemistry , Ruthenium Compounds/pharmacology , Allopurinol/chemistry , Animals , Ascitic Fluid/cytology , Cell Cycle/drug effects , Cell Migration Assays , Cell Survival/drug effects , Cells, Cultured , Female , Fibroblasts , Humans , Mice , Neoplasms, Experimental/drug therapy
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