RESUMEN

The interactions between two Pd complexes, designated as [Pd3(C,N-(C6H4C(Cl) = NO)-4)6] (complex 1) and [Pd3(C12H8C = NO)6] (complex 2), with the human telomeric G-quadruplex DNA, 5'-G3(T2AG3)3-3' (HTG21), were monitored using spectroscopic, biological, and molecular modeling studies. According to the UV-vis results, these complexes can strongly induce and stabilize G-quadruplex DNA structure with Kb1 = 4.5(±0.3) × 106 M-1 and Kb2 = 1.0(±0.2) × 107 M-1via groove mode in comparison with duplex DNA. The release mechanism of the Pd complexes from BSA nanoparticles followed a biphasic pattern unlike that of algal cellulose nanoparticles in vitro. In addition, the cytotoxicity of these complexes on MCF-7 cancer cells and PBMC normal cells was evaluated and compared with cisplatin under similar experimental conditions. Furthermore, to determine and verify the interaction mode of these compounds with G-quadruplex, the molecular docking technique was also performed. Our data clearly demonstrated that complex 2 had higher activity and cytotoxicity than that of complex 1 and could be further investigated in the future as a drug discovery platform.

Asunto(s)

Antineoplásicos/farmacología , ADN de Neoplasias/efectos de los fármacos , G-Cuádruplex/efectos de los fármacos , Compuestos Organometálicos/farmacología , Oximas/farmacología , Paladio/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Sitios de Unión/efectos de los fármacos , Bovinos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Celulosa/química , Chlorophyta/química , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Leucocitos Mononucleares/efectos de los fármacos , Ligandos , Células MCF-7 , Estructura Molecular , Nanopartículas/química , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/química , Oximas/química , Paladio/química , Tamaño de la Partícula , Albúmina Sérica Bovina/química , Propiedades de Superficie , Termodinámica