Photochromic Indolyl Fulgimides as Chromo-pharmacophores Targeting Sirtuins

The Journal of Organic Chemistry
Nadja A SimethBurkhard König

Abstract

Sirtuins are involved in epigenetic regulation, the pathogenesis of cancer, and several metabolic and neurodegenerative diseases. Despite being a promising drug target, only one small molecule passed class II clinical trials to date. Deriving a better mechanistic understanding is hence crucial to find new modulators. We previously reported on a series of dithienyl maleimides as photochromic tool compounds. However, their photochromic behavior was limited. To improve the interconversion and stability of both photoisomers, we replaced the dithienyl maleimide with a fulgimide as a photochromic core to result in biologically active compounds reversibly addressable with purple and orange light. We characterize the obtained compounds regarding their spectroscopic properties, their photostability, and binding characteristics toward sirtuins resulting in a fully remote-controllable Sirtuin modulator using visible light as the external stimulant.

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Citations

Sep 29, 2018·Organic & Biomolecular Chemistry·Karin RustlerBurkhard König
Mar 30, 2019·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·Miriam SchehrRainer Herges
Apr 21, 2020·Chemistry : a European Journal·Karin RustlerBurkhard König
Jun 8, 2021·Chemical Science·Ilse M WellemanWiktor Szymański
Jul 17, 2021·Angewandte Chemie·Oleg BabiiAnne S Ulrich
Oct 1, 2021·Chemical Society Reviews·Jana VolarićBen L Feringa

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