RESUMEN
Oxovanadium(IV) complexes [VO(Fc-tpy)(acac)](ClO4) (1), [VO(Fc-tpy)(nap-acac)](ClO4) (2), [VO(Fc-tpy)(py-acac)](ClO4) (3) and [VO(Ph-tpy)(py-acac)](ClO4) (4) of 4'-ferrocenyl-2,2':6',2"-terpyridine (Fc-tpy) and 4'-phenyl-2,2':6',2"-terpyridine (Ph-tpy) having monoanionic acetylacetonate (acac), naphthylacetylacetonate (nap-acac) or pyrenylacetylacetonate (py-acac) ligand were prepared, characterized and their photocytotoxicity in visible light studied. The ferrocenyl complexes 1-3 showed an intense charge transfer band near 585 nm in DMF and displayed Fc(+)/Fc and V(IV)/V(III) redox couples near 0.66 V and -0.95 V vs. SCE in DMF-0.1 M TBAP. The complexes as avid binders to calf thymus DNA showed significant photocleavage of plasmid DNA in green light (568 nm) forming OH radicals. The complexes that are photocytotoxic in HeLa and MCF-7 cancer cells in visible light (400-700 nm) with low dark toxicity remain nontoxic in normal fibroblast 3T3 cells. ICP-MS and fluorescence microscopic studies show significant cellular uptake of the complexes. Photo-irradiation of the complexes causes apoptotic cell death by ROS as evidenced from the DCFDA assay.
Asunto(s)
Compuestos Ferrosos/química , Hidroxibutiratos/química , Compuestos Organometálicos/farmacología , Pentanonas/química , Fármacos Fotosensibilizantes/farmacología , Piridinas/química , Vanadatos/farmacología , Células 3T3 , Animales , Muerte Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Células HeLa , Humanos , Luz , Células MCF-7 , Metalocenos , Ratones , Estructura Molecular , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/química , Fármacos Fotosensibilizantes/síntesis química , Fármacos Fotosensibilizantes/química , Especies Reactivas de Oxígeno/metabolismo , Relación Estructura-Actividad , Vanadatos/síntesis química , Vanadatos/químicaRESUMEN
Oxovanadium(IV) complexes, viz. [VO(Fc-tpy)(Curc)](ClO4) (1), [VO(Fc-tpy)(bDHC)](ClO4) (2), [VO(Fc-tpy)(bDMC)](ClO4) (3) and [VO(Ph-tpy)(Curc)](ClO4) (4), of 4'-ferrocenyl-2,2':6',2â³-terpyridine (Fc-tpy) and 4'-phenyl-2,2':6',2â³-terpyridine (Ph-tpy) and monoanionic curcumin (Curc), bis-dehydroxycurcmin (bDHC) and bis-demethoxycurcumin (bDMC) were prepared, characterized and their photo-induced DNA cleavage activity and photocytotoxicity in visible light studied. The ferrocenyl complexes 1-3 showed an intense metal-to-ligand charge transfer band near 585 nm in DMF and displayed Fc(+)/Fc and V(IV)/V(III) redox couples near 0.65 V and -1.05 V vs. SCE in DMF-0.1 M TBAP. The complexes as avid binders to calf thymus DNA showed significant photocleavage of plasmid DNA in red light of 647 nm forming OH radicals. The complexes showed photocytotoxicity in HeLa and Hep G2 cancer cells in visible light of 400-700 nm with low dark toxicity. ICP-MS and fluorescence microscopic studies exhibited significant cellular uptake of the complexes within 4 h of treatment with complexes. The treatment with complex 1 resulted in the formation of reactive oxygen species inside the HeLa cells which was evidenced from the DCFDA assay.
