TY  - JOUR
AU  - Krieger, Viktoria
AU  - Hamacher, Alexandra
AU  - Cao, Fangyuan
AU  - Stenzel, Katharina
AU  - Gertzen, Christoph G. W.
AU  - Schäker-Hübner, Linda
AU  - Kurz, Thomas
AU  - Gohlke, Holger
AU  - Dekker, Frank J.
AU  - Kassack, Matthias U.
AU  - Hansen, Finn K.
TI  - Synthesis of peptoid-based class I selective histone deacetylase inhibitors with chemosensitizing properties
JO  - Journal of medicinal chemistry
VL  - 62
IS  - 24
SN  - 1520-4804
CY  - Washington, DC
PB  - ACS
M1  - FZJ-2019-06042
SP  - 11260-11279
PY  - 2019
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:31762274
UR  - <Go to ISI:>//WOS:000505633400020
DO  - DOI:10.1021/acs.jmedchem.9b01489
UR  - https://juser.fz-juelich.de/record/867366
ER  -