Mackenzie Hagemeister, Luke Hamilton, Nicole Wandrey, Mackinzi Hill, Emery Mounce, Noah Mosel, Katie Lytle, Makenna Redinger, Jake Boley, Nathan Fancher, Alexis Haynes, Ianna Fill, Philip A Cole, Evan Hill, Michael Moxley, Allen Thomas
Circadian rhythm (CR) dysregulation negatively impacts health and contributes to mental disorders. The role of melatonin, a hormone intricately linked to CR, is still a subject of active study. The enzyme arylalkylamine N-acetyltransferase (AANAT) is responsible for melatonin synthesis, and it is a potential target for disorders that involve abnormally high melatonin levels, such as seasonal affective disorder (SAD). Current AANAT inhibitors suffer from poor cell permeability, selectivity, and/or potency. To address the latter, we have employed an X-ray crystal-based model to guide the modification of a previously described AANAT inhibitor, containing a rhodanine-indolinone core...
November 20, 2023: ChemMedChem