The mimics of N ε-acyl-lysine derived from cysteine as sirtuin inhibitors

Bioorg Med Chem Lett. 2018 Aug 1;28(14):2375-2378. doi: 10.1016/j.bmcl.2018.06.030. Epub 2018 Jun 18.

Abstract

Sirtuin inhibitors as physiological research tools and therapeutic potentials have caught many attentions in last decades. The mimics of acyl lysine have been approved to be a very efficient strategy for development of mechanism-based sirtuin inhibitors. In current study, a novel scaffold of l-S-(3-carboxamidopropyl) cysteine (l-CAPC) has been exploited for design and synthesis of sirtuin inhibitors. As a result, the mimics of Nε-acyl-lysine derived from cysteine including small molecules (5a-m) and peptides (9a-m) have been synthesized. Among these, the peptides 9g and 9h were found to be the most inhibitory potency and selectivity against SIRT2.

Keywords: Mechanism-based inhibitors; SIRT2 inhibitors; Sirtuin inhibitors; The mimics of lysine; l-Cysteine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cysteine / chemistry
  • Cysteine / pharmacology*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Lysine / analogs & derivatives
  • Lysine / chemistry
  • Lysine / pharmacology*
  • Molecular Structure
  • Sirtuins / antagonists & inhibitors*
  • Sirtuins / metabolism
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Small Molecule Libraries
  • Sirtuins
  • Lysine
  • Cysteine