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@ARTICLE{Raudszus:864927,
author = {Raudszus, Rick and Nowotny, Robert and Gertzen, Christoph
G. W. and Schöler, Andrea and Krizsan, Andor and Gockel,
Ines and Kalwa, Hermann and Gohlke, Holger and Thieme, René
and Hansen, Finn K.},
title = {{F}luorescent analogs of peptoid-based {HDAC} inhibitors:
{S}ynthesis, biological activity and cellular uptake
kinetics},
journal = {Bioorganic $\&$ medicinal chemistry},
volume = {27},
number = {19},
issn = {0968-0896},
address = {Amsterdam [u.a.]},
publisher = {Elsevier},
reportid = {FZJ-2019-04530},
pages = {115039 -},
year = {2019},
abstract = {Fluorescent tagging of bioactive molecules is a powerful
tool to study cellular uptake kinetics and is considered as
an attractive alternative to radioligands. In this study, we
developed fluorescent histone deacetylase (HDAC) inhibitors
and investigated their biological activity and cellular
uptake kinetics. Our approach was to introduce a dansyl
group as a fluorophore in the solvent-exposed cap region of
the HDAC inhibitor pharmacophore model. Three novel
fluorescent HDAC inhibitors were synthesized utilizing
efficient submonomer protocols followed by the introduction
of a hydroxamic acid or 2-aminoanilide moiety as
zinc-binding group. All compounds were tested for their
inhibition of selected HDAC isoforms, and docking studies
were subsequently performed to rationalize the observed
selectivity profiles. All HDAC inhibitors were further
screened in proliferation assays in the esophageal
adenocarcinoma cell lines OE33 and OE19. Compound 2,
6-((N-(2-(benzylamino)-2-oxoethyl)-5-(dimethylamino)naphthalene)-1-sulfonamido)-N-hydroxyhexanamide,
displayed the highest HDAC inhibitory capacity as well as
the strongest anti-proliferative activity. Fluorescence
microscopy studies revealed that compound 2 showed the
fastest uptake kinetic and reached the highest absolute
fluorescence intensity of all compounds. Hence, the rapid
and increased cellular uptake of 2 might contribute to its
potent anti-proliferative properties.},
cin = {JSC / NIC / ICS-6},
ddc = {610},
cid = {I:(DE-Juel1)JSC-20090406 / I:(DE-Juel1)NIC-20090406 /
I:(DE-Juel1)ICS-6-20110106},
pnm = {511 - Computational Science and Mathematical Methods
(POF3-511) / Forschergruppe Gohlke $(hkf7_20170501)$},
pid = {G:(DE-HGF)POF3-511 / $G:(DE-Juel1)hkf7_20170501$},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:31420257},
UT = {WOS:000484396400008},
doi = {10.1016/j.bmc.2019.07.055},
url = {https://juser.fz-juelich.de/record/864927},
}