Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
Assessment of the trifluoromethyl ketone functionality as an alternative zinc-binding group for selective HDAC6 inhibitionElectronic supplementary information (ESI) available. See DOI: 10.1039/c8md00107c
Erscheinungsjahr
2018-06
Quelle
Alma/SFX Local Collection
Beschreibungen/Notizen
Recent studies point towards the possible disadvantages of using hydroxamic acid-based zinc-binding groups in HDAC inhibitors due to
e.g.
mutagenicity issues. In this work, we elaborated on our previously developed Tubathian series, a class of highly selective thiaheterocyclic HDAC6 inhibitors, by replacing the benzohydroxamic acid function by an alternative zinc chelator,
i.e.
, an aromatic trifluoromethyl ketone. Unfortunately, these compounds showed a reduced potency to inhibit HDAC6 as compared to their hydroxamic acid counterparts. In agreement, the most active trifluoromethyl ketone was unable to influence the growth of SK-OV-3 ovarian cancer cells nor to alter the acetylation status of tubulin and histone H3. These data suggest that replacement of the zinc-binding hydroxamic acid function with a trifluoromethyl ketone zinc-binding moiety within reported benzohydroxamic HDAC6 inhibitors should not be considered as a standard strategy in HDAC inhibitor development.
The replacement of the hydroxamic acid zinc-binding group in benzohydroxamic acid HDAC6 inhibitors by a trifluoromethyl ketone function leads to severe reduction in enzymatic and cellular activity.
Sprache
Englisch
Identifikatoren
ISSN: 2040-2503
eISSN: 2040-2511
DOI: 10.1039/c8md00107c
Titel-ID: cdi_rsc_primary_c8md00107c
Format
–
Weiterführende Literatur
Empfehlungen zum selben Thema automatisch vorgeschlagen von bX