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A Photoactivatable Version of Ivabradine Enables Light-Induced Block of HCN Current In Vivo

2024; American Chemical Society; Volume: 67; Issue: 18 Linguagem: Inglês

10.1021/acs.jmedchem.4c01047

1520-4804

Alessandro Porro, Edoardo Armano, Federico Brandalise, Rebecca Appiani, Mônica Beltrame, Andrea Saponaro, Clelia Dallanoce, Koichi Nakajo, K.S. Ryu, R. Leone, Gerhard Thiel, Marco Pallavicini, Anna Moroni, Cristiano Bolchi,

Coenzyme Q10 studies and effects

Therapeutic drugs, whose bioactivity is hindered by a photoremovable cage, offer the advantage of spatiotemporal confinement of their action to the target diseased tissue with improved bioavailability and efficacy. Here, we have applied such an approach to ivabradine (IVA), a bradycardic agent indicated for angina pectoris and heart failure, acting as a specific HCN channel blocker. To overcome the side effects due to its poor discrimination among HCN channel subtypes (HCN1-4), we prepared a caged version of IVA linked to a photocleavable bromoquinolinylmethyl group (BHQ-IVA). We show that upon illumination with blue light (440 nm), BHQ-IVA releases active IVA that blocks HCN channel currents