RESUMEN
Proteases are excellent biomarkers for a variety of diseases, offer multiple opportunities for diagnostic applications and are valuable targets for therapy. From a chemistry-based perspective this review discusses and critiques the most recent advances in the field of substrate-based probes for the detection and analysis of proteolytic activity both in vitro and in vivo.
Asunto(s)
Péptido Hidrolasas , Péptidos , Biomarcadores , Péptido Hidrolasas/metabolismo , Péptidos/metabolismo , ProteolisisRESUMEN
A ruthenium-based mitochondrial-targeting photosensitiser that undergoes efficient cell uptake, enables the rapid catalytic conversion of PtIV prodrugs into their active PtII counterparts, and drives the generation of singlet oxygen was designed. This dual mode of action drives two orthogonal cancer-cell killing mechanisms with temporal and spatial control. The designed photosensitiser was shown to elicit cell death of a panel of cancer cell lines including those showing oxaliplatin-resistance.
Asunto(s)
Antineoplásicos/farmacología , Compuestos Organoplatinos/farmacología , Fármacos Fotosensibilizantes/farmacología , Profármacos/farmacología , Oxígeno Singlete/metabolismo , Antineoplásicos/síntesis química , Antineoplásicos/química , Catálisis , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Estructura Molecular , Compuestos Organoplatinos/síntesis química , Compuestos Organoplatinos/química , Procesos Fotoquímicos , Fotoquimioterapia , Fármacos Fotosensibilizantes/síntesis química , Fármacos Fotosensibilizantes/química , Profármacos/síntesis química , Profármacos/química , Oxígeno Singlete/químicaRESUMEN
The term electroceutical has been used to describe implanted devices that deliver electrical stimuli to modify biological function. Herein, we describe a new concept in electroceuticals, demonstrating for the first time the electrochemical activation of metal-based prodrugs. This is illustrated by the controlled activation of Pt(iv) prodrugs into their active Pt(ii) forms within a cellular context allowing selectivity and control of where, when and how much active drug is generated.