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

Abstract

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).

Preparation of new half sandwich ruthenium arene complexes with aminophosphines as potential chemotherapeutics

“…The conformational changes in the plasmid DNA structure induced by these compounds may presumably be attributed to covalent interactions between ruthenium and DNA. These interactions are similar to those induced by cisplatin or cisplatinum(II) analogues [70][71][72][73] and very different to those observed for classical intercalators such as ethydium bromide and other planar heterocycles [74,75]. Finally, it is important to highlight that both compounds were able to produce some fragmentation of DNA chains during the reaction, even in the absence of an activator.…”

Palladium(II) binding to N(7) of acyclovir: DNA interaction and herpes simplex virus (HSV-1) inhibitory activity

“…Accordingly, side-by-side association of the resulting aggregated DNA segments leads to condensing loops in process of aggregation and rods. After longer period of time the image (d) taken after 3 h post-incubation shows these aggregates transformed into spheres as a consequence of the strong interaction between Pd(II)-ACV and DNA [50,51]. Contrary to ACV, supercoiled forms of the plasmid DNA derives from the strong effect of Pd(II)-ACV and indicates that Pd originates deeper changes in the structure of the plasmid.…”

Synthesis, spectral and thermal studies of some polymeric mixed ligand uracil–hydrazide complexes with transition metal ions

“…The antitumor activity of platinum(II) complexes with nucleosides and their bases have been investigated extensively [15][16][17]. It is accepted that the antitumor activity is due to inhibition of DNA synthesis in cancer cells [18,19].…”