Nε-Thioacetyl-Lysine-Containing Tri-, Tetra-, and Pentapeptides as SIRT1 and SIRT2 Inhibitors

N-epsilon-Thioacetyl-lysine-containing tri-, tetra-, and pentapeptides, based on the (x-tubulin and p53 protein sequences, were studied as SIRT1 and SIRT2 inhibitors. The potency of the pentapeptides depended on the selection of the side chains. The removal of N- and C-terminal residues of the pentapeptides; yielded tripeptides with retained SIRT1 inhibitory activity but decreased SIRT2 inhibitory activity. The most potent SIRT1 inhibitors were equipotent with the reference compound (6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide) with the IC50 values of 180-330 nM.