Journal Article

FZJ-2019-06042

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Synthesis of peptoid-based class I selective histone deacetylase inhibitors with chemosensitizing properties

Krieger, V. ; Hamacher, A. ; Cao, F. ; Stenzel, K. ; Gertzen, C. G. W.FZJ* ; Schäker-Hübner, L. ; Kurz, T. ; Gohlke, H.FZJ* ; Dekker, F. J. ; Kassack, M. U. (Corresponding author) ; Hansen, F. K. (Corresponding author)

2019
ACS Washington, DC

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Please use a persistent id in citations: doi:10.1021/acs.jmedchem.9b01489

Abstract: There is increasing evidence that histone deacetylase (HDAC) inhibitors can (re)sensitize cancer cells for chemotherapeutics via ‘epigenetic priming’. In this work, we describe the synthesis of a series of class I selective HDAC inhibitors with 2-aminoanilides as zinc-binding groups. Several of the synthesized compounds revealed potent inhibition of the class I HDAC isoforms HDAC1, 2 and/or 3 and promising antiproliferative effects in the human ovarian cancer cell line A2780 and the human squamous carcinoma cell line Cal27. Selected compounds were investigated in a cellular model of platinum resistance. In particular compound 2a revealed potent chemosensitizing properties and full reversal of cisplatin resistance in Cal27CisR cells. This effect is related to a synergistic increase in caspase 3/7 activation and induction of apoptosis. Thus, this work demonstrates that pan-HDAC inhibition or dual class I/class IIb inhibition is not required for full reversal of cisplatin resistance.

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Contributing Institute(s):

1. John von Neumann - Institut für Computing (NIC)
2. Jülich Supercomputing Center (JSC)
3. Strukturbiochemie (ICS-6)

Research Program(s):

1. 511 - Computational Science and Mathematical Methods (POF3-511) (POF3-511)
2. Forschergruppe Gohlke (hkf7_20170501) (hkf7_20170501)

Appears in the scientific report 2019

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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