Exploration of novel macrocyclic dipeptide N-benzyl amides as proteasome inhibitors. Academic Article uri icon

Overview

abstract

  • As proteasome inhibitors, a series of novel macrocyclic dipeptide N-benzyl amides were designed, synthesized and evaluated. Most of them exhibited potent proteasome inhibition and excellent anti-proliferative activity against RPMI 8226, MM1S, and MV-4-11 cell lines. As the most distinguished one among this series, compound 23h displayed potent and selective proteasome inhibitory potency (IC50: β5c = 29 nM, β5i = 35 nM, β1c, β2c,β1i,β2i > 10 μM), excellent anti-proliferative activity against RPMI 8226, MM1S, and MV-4-11 cell lines with IC50 values of 18 nM, 15 nM, and 21 nM, respectively, as well as favorable metabolic stability in human liver microsomes (HLMs), highlighting that it is a promising lead compound for further development of proteasome inhibitors.

publication date

  • December 31, 2018

Research

keywords

  • Drug Design
  • Macrocyclic Compounds
  • Proteasome Inhibitors

Identity

Scopus Document Identifier

  • 85059342558

Digital Object Identifier (DOI)

  • 10.1016/j.ejmech.2018.12.072

PubMed ID

  • 30611983

Additional Document Info

volume

  • 164