Human SIRT3 tripeptidic inhibitors containing N(ε)-thioacetyl-lysine.

Built upon our lead pan-SIRT1/2/3 tripeptidic inhibitors that contain the catalytic mechanism-based sirtuin inhibitory warhead N(ε)-thioacetyl-lysine, three of their analogs (i.e., 7, 9, and 19) were discovered in the current study to exhibit a significantly enhanced SIRT3 inhibitory selectivity while maintaining the SIRT3 inhibitory potency. These compounds represent novel lead compounds for developing more potent and selective SIRT3 inhibitors of the catalytic mechanism-based type.