RESUMO
New Pt(ii) and Pd(ii) complexes with the metal center coordinated to two different chelating ligands, tropolone (trop) and dihexadecyl-2,2'-bipyridine-4,4'-dicarboxylate bipyridine (bipy), [(bipy)M(trop)][CF(3)SO(3)], have been synthesized and their biological evaluation has been performed demonstrating a remarkable cytotoxic activity in vitro against the human prostate DU145 and hormone-sensitive LNCaP cells lines. Moreover, for the Pt(ii) derivative, the molecular structure has been determined by single-crystal X-ray diffraction and computational analysis on the hydrolysis reaction mechanisms have been performed by density functional theory (DFT) calculations, in order to correlate molecular structure, biological activity and mechanism of action of this new class of complexes based on two different bioactive fragments.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Paládio/química , Compostos de Platina/química , Compostos de Platina/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Humanos , Hidrólise , Concentração Inibidora 50 , Modelos Moleculares , Estrutura MolecularRESUMO
The first examples of binuclear and mononuclear ortho-palladated complexes based on a functionalized 2-phenylquinoline ligand have been synthesized and fully characterized. Conjugating cyclopalladated fragments to curcumin family biologically active beta-diketones gives in one single molecule two different functionalities. The structural variations based on the curcuminoid structure have been tested for their in vitro cytotoxic activity. The activity of complexes comprised of a cyclopalladated fragment conjugated to functionalized bioactive ligands, represents the potential of organometallic systems in generating new bifunctional biomaterials.
Assuntos
Curcumina/química , Compostos Organometálicos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , Humanos , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/farmacologiaRESUMO
The synthesis and the characterization (elemental analysis, (1)H NMR and X-ray) of the first cyclopalladated complexes containing 4-hydroxyacridinate as complementary ligand are described. 4-Hydroxyacridine acts as a bidentate [N,O] chelating ligand, giving rise to square planar Pd(II) complexes in the coordination of a cyclopalladated fragment of phenylpyridine or phenylpyrimidine, characterized by the presence of two almost coplanar metalated rings. The biological activity studies conducted on these new Pd(II) complexes proved that the phenylpyridine Pd(II) derivative is more efficient than cis-platinum. The intrinsically substitutional inertness of the cyclopalladated ring and the presence of the [N,O] chelated acridine ligand make these systems of particular interest in their promising biological activity.