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Dithiobiureas Palladium(II) complexes' studies: From their synthesis to their biological action
Jorge M Herrero1, David Fabra2, Ana I Matesanz2
1Departamento de Bioquímica, Facultad de Medicina and Instituto de Investigaciones Biomédicas Albert Sols, Universidad Autónoma de Madrid, 28029 Madrid, Spain; Cancer Stem Cell and Fibroinflammatory Microenvironment Group, Chronic Diseases and Cancer Area 3 -Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.
Abstract:
Dithiobiureas coordination chemistry towards palladium (II) ions and their possible application is presented and discussed. 1,6-(4-Methoxyphenyl)-2,5-dithiobiurea and 1,6-(4-chlorophenyl)-2,5-dithiobiurea afford two Pd(II) complexes with the general formula [Pd2(H2L)Cl2(PPh3)2]. The metal ion forms one chelate ring with the dithiobiurea, and binds to a triphenylphosphine and an additional leaving group cisplatin like. One of the complexes (1) is endowed not only with stability in DMSO and aqua solutions containing a biological buffer but also with cytotoxicity versus gastric cancer cell lines. Complex 1 does not interact covalently to DNA models, neither activates p53 or Checkpoint Kinase 1 key proteins for DNA damage response. Thus, we propose that complex 1 exerts its action by activating Mitogen-Activated Protein Kinases [p38, Extracellular signal-regulated kinases (ERKs), c-Jun N-terminal kinases (JNKs)] as cell death inductors.
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