RESUMEN
Organic-metal complexes are promising molecules for use in photodynamic therapy (PDT). The aim of this study was to investigate in vitro effects of novel Ru(ii) and Ir(iii) BODIPY complexes for PDT. These hybrid organic-metal molecules (Ru-BD and Ir-BD) have been synthesized via reactions of a BODIPY precursor (BD) with a phenanthroline unit bearing Ru(ii) (3) and novel Ir(iii) (4) compounds. The crystal structures of the new distyryl BODIPY (BD) and Ru(ii) complex (3) are also reported. The photophysical and singlet oxygen generation properties of Ru-BD and Ir-BD were investigated in comparison with unsubstituted BODIPY (BD). Moreover, Ru-BD and Ir-BD have been biologically evaluated in vitro in chronic myeloid leukemia and cervical cancer cell lines in terms of photodynamic therapy efficacy in the presence of BD control. These complexes were not toxic in the dark but red light was needed to induce cell death. These data support the fact that Ru-BD could be accepted as a valuable photosensitizer-drug for further PDT treatment.
Asunto(s)
Antineoplásicos/farmacología , Compuestos de Boro/farmacología , Colorantes/farmacología , Compuestos Organometálicos/farmacología , Fotoquimioterapia , Fármacos Fotosensibilizantes/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Compuestos de Boro/síntesis química , Compuestos de Boro/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Colorantes/síntesis química , Colorantes/química , Cristalografía por Rayos X , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Iridio/química , Iridio/farmacología , Modelos Moleculares , Estructura Molecular , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/química , Fármacos Fotosensibilizantes/síntesis química , Fármacos Fotosensibilizantes/química , Rutenio/química , Rutenio/farmacología , Oxígeno Singlete/análisis , Oxígeno Singlete/metabolismo , Células Tumorales CultivadasRESUMEN
In this paper, we describe an efficient InCl3-catalyzed two-component reaction of 1-(2-aminophenyl)pyrroles/indoles and 2-propargyloxybenzaldehydes for the direct synthesis of 12bH-benzo[6,7]1,4-oxazepino[4,5-a]pyrrolo/indolo[2,1-c]quinoxalines. This high atom- and step-economical one-pot process generates three new C/N-C bonds in a single synthetic operation, resulting in the formation of new six- and seven-membered heterocyclic rings. The easy availability of the starting materials, the use of the relatively inexpensive indium catalyst, and the good substrate scope are the salient features of this strategy. The proposed mechanistic pathway involves imine formation, two consecutive cyclizations via electrophilic aromatic substitution and nucleophilic addition reactions, and the H shift step.