Identification of a sirtuin 3 inhibitor that displays selectivity over sirtuin 1 and 2

As part of an effort to identify novel selective modulators of sirtuins, we synthesized and tested several isosteres and constrained analogues of nicotinamide. Biological data suggest that compound 2 is selective for Sirt3 over Sirt1 and Sirt2.

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► Rigid analogues and isosteres of nicotinamide have been synthesized.
► Obtained compounds were tested to evaluate their cellular effects and sirtuin inhibition.
► The 3-triazolylpyridine inhibits selectively Sirt3 over Sirt1 and Sirt2.