Palladium(II) and platinum(II) organometallic complexes with the model nucleobase anions of thymine, uracil, and cytosine: antitumor activity and interactions with DNA of the platinum compounds.
Pd(II) and Pt(II) complexes with the anions of the model nucleobases 1-methylthymine (1-MethyH), 1-methyluracil (1-MeuraH), and 1-methylcytosine (1-MecytH) of the types [Pd(dmba)(mu-L)]2 [dmba = N,C-chelating 2-((dimethylamino)methyl)phenyl; L = 1-Methy, 1-Meura or 1-Mecyt] and [M(dmba)(L)(L')] [L = 1-Methy or 1-Meura; L' = PPh(3) (M = Pd or Pt), DMSO (M = Pt)] have been obtained. Palladium complexes of the types [Pd(C6F5)(N-N)(L)] [L = 1-Methy or 1-Meura; N-N = N,N,N',N'-tetramethylethylenediamine (tmeda), 2,2'-bipyridine (bpy), or 4,4'-dimethyl-2,2'-bipyridine (Me2bpy)] and [NBu4][Pd(C6F5)(1-Methy)2(H2O)] have also been prepared. The crystal structures of [Pd(dmba)(mu-1-Methy)]2, [Pd(dmba)(mu-1-Mecyt)]2.2CHCl3, [Pd(dmba)(1-Methy)(PPh3)].3CHCl3, [Pt(dmba)(1-Methy)(PPh3)], [Pd(tmeda)(C6F5)(1-Methy)], and [NBu4][Pd(C6F5)(1-Methy)2(H2O)].H2O have been established by X-ray diffraction. The DNA adduct formation of the new platinum complexes synthesized was followed by circular dichroism and electrophoretic mobility. Atomic force microscopy images of the modifications caused by the platinum complexes on plasmid DNA pBR322 were also obtained. Values of IC50 were also calculated for the new platinum complexes against the tumor cell line HL-60. All the new platinum complexes were more active than cisplatin (up to 20-fold in some cases).
Ruiz
José
J
Departamento de Química Inorganica, Universidad de Murcia, 30071-Murcia, Spain. jruz@um.es
Lorenzo
Julia
J
Sanglas
Laura
L
Cutillas
Natalia
N
Vicente
Consuelo
C
Villa
María Dolores
MD
Avilés
Francesc X
FX
López
Gregorio
G
Moreno
Virtudes
V
Pérez
José
J
Bautista
Delia
D
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D003596:Cytosine / Q000737:chemistry* / Q000494:pharmacology; D004247:DNA / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000494:pharmacology*; D010165:Palladium / Q000737:chemistry / Q000494:pharmacology*; D013941:Thymine / Q000737:chemistry* / Q000494:pharmacology
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D010165:Palladium; D003596:Cytosine; D004247:DNA; D013941:Thymine