title: Synthesis, characterization and biological activity of trans-platinum(II) and trans-platinum(IV) complexes with 4-hydroxymethylpyridine.
abstract: The synthesis and chemical characterization of two new trans platinum complexes, trans-[PtCl(2)NH(3)(4-hydroxymethylpyridine)] (1) and trans-[PtCl(4)NH(3)(4-hydroxymethylpyridine)] (2) are described. Their ability to interact with 5'-GMP by themselves and in the presence of reducing agents in the case of trans-[PtCl(4)NH(3)(4-hydroxymethylpyridine)] were tested. Circular dichroism, electrophoretic mobility in agarose gel, and atomic force microscopy studies showed that the interaction of complex 1 with DNA is stronger than that of complex 2. Cytotoxicity tests against HL-60 tumor cells also showed higher activity for trans-[PtCl(2)NH(3)(4-hydroxymethylpyridine)] than for trans-[PtCl(4)NH(3)(4-hydroxymethylpyridine)]. Complex 1 presents similar behavior to cisplatin, but with a lower IC(50) at 24 h. Complex 1 also showed high apoptosis induction.
authors.affiliation: Departament de Química Inorgánica, Universitat de Barcelona, Diagonal 647, 08028 Barcelona, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Martínez
authors.forename: Julia
authors.initials: J
authors.lastname: Lorenzo
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Prieto
authors.forename: Rafael
authors.initials: R
authors.lastname: de Llorens
authors.forename: Mercè
authors.initials: M
authors.lastname: Font-Bardia
authors.forename: Xavier
authors.initials: X
authors.lastname: Solans
authors.forename: Francesc X
authors.initials: FX
authors.lastname: Avilés
authors.forename: Virtudes
authors.initials: V
authors.lastname: Moreno
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D006157:Guanosine Monophosphate / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D018625:Microscopy, Atomic Force; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017671:Platinum Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: C507745:4-hydroxymethylpyridine; D009944:Organoplatinum Compounds; D017671:Platinum Compounds; D011725:Pyridines; C507746:trans-PtCl(2)NH(3)(4-hydroxymethylpyridine); D014867:Water; D006157:Guanosine Monophosphate; D004247:DNA