Activation of Sirtuin 2 Inhibitors Employing Photoswitchable Geometry and Aqueous Solubility.

ABSTRACT: Because isoenzymes of the experimentally and therapeutically extremely relevant sirtuin family show high similarity, addressing the unique selectivity pocket of sirtuin 2 is a promising strategy towards selective inhibitors. An unrelated approach towards selective inhibition of isoenzymes with varied tissue distribution is targeted drug delivery or spatiotemporal activation by photochemical activation. Azologization of two nicotinamide-mimicking lead structures was undertaken to combine both approaches and yielded a set of 33 azobenzenes and azopyridines that have been evaluated for their photochemical behaviour and bioactivity. For some compounds, inhibitory activity reached the sub-micromolar range in their thermodynamically favoured E form and could be decreased by photoisomerization to

SUBMITTER: Grathwol CW 

PROVIDER: S-EPMC7496931 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature