%0 Journal Article
%A Krieger, Viktoria
%A Hamacher, Alexandra
%A Cao, Fangyuan
%A Stenzel, Katharina
%A Gertzen, Christoph G. W.
%A Schäker-Hübner, Linda
%A Kurz, Thomas
%A Gohlke, Holger
%A Dekker, Frank J.
%A Kassack, Matthias U.
%A Hansen, Finn K.
%T Synthesis of peptoid-based class I selective histone deacetylase inhibitors with chemosensitizing properties
%J Journal of medicinal chemistry
%V 62
%N 24
%@ 1520-4804
%C Washington, DC
%I ACS
%M FZJ-2019-06042
%P 11260-11279
%D 2019
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:31762274
%U <Go to ISI:>//WOS:000505633400020
%R 10.1021/acs.jmedchem.9b01489
%U https://juser.fz-juelich.de/record/867366