Photochromic Indolyl Fulgimides as Chromo-pharmacophores Targeting Sirtuins

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.