Synthesis, characterization and biological activity of trans-platinum(II) and trans-platinum(IV) complexes with 4-hydroxymethylpyridine.
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.
Martínez
Alberto
A
Departament de Química Inorgánica, Universitat de Barcelona, Diagonal 647, 08028 Barcelona, Spain.
Lorenzo
Julia
J
Prieto
Maria J
MJ
de Llorens
Rafael
R
Font-Bardia
Mercè
M
Solans
Xavier
X
Avilés
Francesc X
FX
Moreno
Virtudes
V
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
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