RESUMO
We describe the synthesis and biological testing of ruthenium-bipyridine ruxolitinib (RuBiRuxo), a photoreleasable form of ruxolitinib, a JAK inhibitor used as an antitumoral agent in cutaneous T-cell lymphomas (CTCL). This novel caged compound is synthesized efficiently, is stable in aqueous solution at room temperature, and is photoreleased rapidly by visible light. Irradiation of RuBiRuxo reduces cell proliferation and induces apoptosis in a light- and time-dependent manner in a CTCL cell line. This effect is specific and is mediated by a decreased phosphorylation of STAT proteins. Our results demonstrate the potential of ruthenium-based photocompounds and light-based therapeutic approaches for the potential treatment of cutaneous lymphomas and other pathologies.
Assuntos
Antineoplásicos , Apoptose , Proliferação de Células , Nitrilas , Pirazóis , Pirimidinas , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Proliferação de Células/efeitos dos fármacos , Nitrilas/química , Nitrilas/farmacologia , Nitrilas/síntese química , Pirimidinas/química , Pirimidinas/farmacologia , Pirimidinas/síntese química , Apoptose/efeitos dos fármacos , Pirazóis/farmacologia , Pirazóis/química , Pirazóis/síntese química , Linhagem Celular Tumoral , Inibidores de Janus Quinases/farmacologia , Inibidores de Janus Quinases/química , Inibidores de Janus Quinases/síntese química , Rutênio/química , Rutênio/farmacologia , Luz , Estrutura Molecular , Janus Quinases/antagonistas & inibidores , Janus Quinases/metabolismoRESUMO
We introduce a new caged glutamate, based in a ruthenium bipyridyl core, that undergoes heterolytic cleavage after irradiation with visible light with wavelengths up to 532nm, yielding free glutamate in less than 50ns. Glutamate photorelease occurs also efficiently following two-photon (2P) excitation at 800nm, and has a functional cross section of 0.14GM.