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1000 Titel
  • Structural Modifications Yield Novel Insights Into the Intriguing Pharmacodynamic Potential of Anti-inflammatory Nitro-Fatty Acids
1000 Autor/in
  1. Hellmuth, Nadine |
  2. Brat, Camilla |
  3. Awad, Omar |
  4. George, Sven |
  5. Kahnt, Astrid |
  6. Bauer, Tom |
  7. Huynh Phuoc, Hai Phong |
  8. Steinhilber, Dieter |
  9. Angioni, Carlo |
  10. Hassan, Mohamed |
  11. Hock, Katharina J. |
  12. Manolikakes, Georg |
  13. Zacharowski, Kai |
  14. Roos, Jessica |
  15. Maier, Thorsten Jürgen |
1000 Erscheinungsjahr 2021
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2021-11-18
1000 Erschienen in
1000 Quellenangabe
  • 12:715076
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2021
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.3389/fphar.2021.715076 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8637440/ |
1000 Ergänzendes Material
  • https://www.frontiersin.org/articles/10.3389/fphar.2021.715076/full#h11 |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Endogenous nitro-fatty acids (NFA) are potent electrophilic lipid mediators that exert biological effects in vitro and in vivo via selective covalent modification of thiol-containing target proteins. The cytoprotective, anti-inflammatory, and anti-tumorigenic effects of NFA in animal models of disease caused by targeted protein nitroalkylation are a valuable basis for the development of future anti-phlogistic and anti-neoplastic drugs. Considering the complexity of diseases and accompanying comorbidities there is an urgent need for clinically effective multifunctional drugs. NFA are composed of a fatty acid backbone containing a nitroalkene moiety triggering Michael addition reactions. However, less is known about the target-specific structure–activity relationships and selectivities comparing different NFA targets. Therefore, we analyzed 15 NFA derivatives and compared them with the lead structure 9-nitro-oleic acid (9NOA) in terms of their effect on NF-κB (nuclear factor kappa B) signaling inhibition, induction of Nrf-2 (nuclear factor erythroid 2-related factor 2) gene expression, sEH (soluble epoxide hydrolase), LO (lipoxygenase), and COX-2 (cyclooxygenase-2) inhibition, and their cytotoxic effects on colorectal cancer cells. Minor modifications of the Michael acceptor position and variation of the chain length led to drugs showing increased target preference or enhanced multi-targeting, partly with higher potency than 9NOA. This study is a significant step forward to better understanding the biology of NFA and their enormous potential as scaffolds for designing future anti-inflammatory drugs.
1000 Sacherschließung
lokal NF-κB
lokal structure-function
lokal cyclooxygenase-2
lokal soluble epoxide hydrolase
lokal Nrf-2
gnd 4174134-1 Pharmakodynamik
lokal michael acceptor
lokal 5-lipoxygenase
lokal nitroalkene
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/uri/SGVsbG11dGgsIE5hZGluZQ==|https://frl.publisso.de/adhoc/uri/QnJhdCwgQ2FtaWxsYQ==|https://frl.publisso.de/adhoc/uri/QXdhZCwgT21hcg==|https://frl.publisso.de/adhoc/uri/R2VvcmdlLCBTdmVu|https://frl.publisso.de/adhoc/uri/IEthaG50LCBBc3RyaWQ=|https://frl.publisso.de/adhoc/uri/QmF1ZXIsIFRvbQ==|https://frl.publisso.de/adhoc/uri/SHV5bmggUGh1b2MsIEhhaSBQaG9uZw==|https://frl.publisso.de/adhoc/uri/U3RlaW5oaWxiZXIsIERpZXRlcg==|https://frl.publisso.de/adhoc/uri/QW5naW9uaSwgQ2FybG8=|https://frl.publisso.de/adhoc/uri/SGFzc2FuLCBNb2hhbWVk|https://frl.publisso.de/adhoc/uri/SG9jaywgS2F0aGFyaW5hIEou|https://frl.publisso.de/adhoc/uri/TWFub2xpa2FrZXMsIEdlb3Jn|https://frl.publisso.de/adhoc/uri/WmFjaGFyb3dza2ksIEthaQ==|https://d-nb.info/gnd/1053809271|https://orcid.org/0000-0003-3234-947X
1000 Label
1000 Förderer
  1. Deutsche Forschungsgemeinschaft |
1000 Fördernummer
  1. MA-5825/1-2
1000 Förderprogramm
  1. -
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Deutsche Forschungsgemeinschaft |
    1000 Förderprogramm -
    1000 Fördernummer MA-5825/1-2
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6431866.rdf
1000 Erstellt am 2022-03-01T14:36:10.475+0100
1000 Erstellt von 323
1000 beschreibt frl:6431866
1000 Bearbeitet von 25
1000 Zuletzt bearbeitet 2022-03-15T07:52:14.520+0100
1000 Objekt bearb. Tue Mar 15 07:51:37 CET 2022
1000 Vgl. frl:6431866
1000 Oai Id
  1. oai:frl.publisso.de:frl:6431866 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
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