Rational design and diversity-oriented synthesis of peptoid-based selective HDAC6 inhibitors

D Diedrich; A Hamacher; C G W Gertzen; L A Alves Avelar; G J Reiss; T Kurz; H Gohlke; M U Kassack; F K Hansen

doi:10.1039/c5cc10301k

Rational design and diversity-oriented synthesis of peptoid-based selective HDAC6 inhibitors

Chem Commun (Camb). 2016 Feb 21;52(15):3219-22. doi: 10.1039/c5cc10301k.

Authors

D Diedrich¹, A Hamacher¹, C G W Gertzen¹, L A Alves Avelar¹, G J Reiss², T Kurz¹, H Gohlke¹, M U Kassack¹, F K Hansen¹

Affiliations

¹ Institut für Pharmazeutische und Medizinische Chemie, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany. [email protected].
² Institut für Anorganische Chemie und Strukturchemie, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany.

PMID: 26810607
DOI: 10.1039/c5cc10301k

Abstract

A mini library of HDAC inhibitors with peptoid-based cap groups was synthesized using an efficient multicomponent approach. Four compounds were identified as potent HDAC6 inhibitors with a selectivity over other HDAC isoforms. The most potent HDAC6 inhibitor revealed remarkable chemosensitizing properties and completely reverted the cisplatin resistance in Cal27 CisR cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Drug Design
Histone Deacetylase Inhibitors / chemical synthesis*
Histone Deacetylase Inhibitors / chemistry
Histone Deacetylase Inhibitors / pharmacology
Molecular Docking Simulation
Peptoids / chemistry*

Substances

Histone Deacetylase Inhibitors
Peptoids