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J Am Chem Soc ; 146(19): 13317-13325, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38700457

ABSTRACT

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.


Subject(s)
Antineoplastic Agents , Apoptosis , Cell Proliferation , Nitriles , Pyrazoles , Pyrimidines , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Cell Proliferation/drug effects , Nitriles/chemistry , Nitriles/pharmacology , Nitriles/chemical synthesis , Pyrimidines/chemistry , Pyrimidines/pharmacology , Pyrimidines/chemical synthesis , Apoptosis/drug effects , Pyrazoles/pharmacology , Pyrazoles/chemistry , Pyrazoles/chemical synthesis , Cell Line, Tumor , Janus Kinase Inhibitors/pharmacology , Janus Kinase Inhibitors/chemistry , Janus Kinase Inhibitors/chemical synthesis , Ruthenium/chemistry , Ruthenium/pharmacology , Light , Molecular Structure , Janus Kinases/antagonists & inhibitors , Janus Kinases/metabolism
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