Total synthesis and biological evaluation of seven new anti-inflammatory oxacyclododecindione-type macrolactones

Publikationstyp:
Zeitschriftenaufsatz
Metadaten:
Autoren
  • Carina Weber
  • Nina Vierengel
  • Thorsten Walter
  • Torsten Behrendt
  • Tobias Lucas
  • Gerhard Erkel
  • Till Opatz
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000555663000017&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1039/d0ob00958j
eISSN
1477-0539
Externe Identifier
  • Clarivate Analytics Document Solution ID: MU4TT
  • PubMed Identifier: 32691816
ISSN
1477-0520
Ausgabe der Veröffentlichung
30
Zeitschrift
ORGANIC & BIOMOLECULAR CHEMISTRY
Paginierung
5906 - 5917
Datum der Veröffentlichung
2020
Status
Published
Titel
Total synthesis and biological evaluation of seven new anti-inflammatory oxacyclododecindione-type macrolactones
Sub types
  • Article
Ausgabe der Zeitschrift
18

Datenquelle: Web of Science (Lite)

Andere Metadatenquellen:
Abstract
<p>Seven new macrolactones of the oxacyclododecindione family have been synthesized and tested for their inhibitory activity on TGF-β-inducible Smad2/3- as well as IL-4-inducible STAT6-dependent signalling pathways.</p>
Autoren
  • Carina Weber
  • Nina Vierengel
  • Thorsten Walter
  • Torsten Behrendt
  • Tobias Lucas
  • Gerhard Erkel
  • Till Opatz
DOI
10.1039/d0ob00958j
eISSN
1477-0539
ISSN
1477-0520
Ausgabe der Veröffentlichung
30
Zeitschrift
Organic &amp; Biomolecular Chemistry
Sprache
en
Online publication date
2020
Paginierung
5906 - 5917
Status
Published online
Herausgeber
Royal Society of Chemistry (RSC)
Herausgeber URL
http://dx.doi.org/10.1039/d0ob00958j
Datum der Datenerfassung
2024
Titel
Total synthesis and biological evaluation of seven new anti-inflammatory oxacyclododecindione-type macrolactones
Ausgabe der Zeitschrift
18

Datenquelle: Crossref

Abstract
Through variation of our previously published total synthesis of two highly active anti-inflammatory macrolactones from the oxacyclododecindione family (J. Tauber, M. Rohr, T. Walter, G. Erkel and T. Opatz, Org. Biomol. Chem., 2015, 13, 7813-7821), seven new representatives of this compound class were prepared. Substitution of the 14-hydroxy group in oxacyclododecindione with a methyl substituent provided a readily accessible non-natural analogue which has similar pharmacological properties to the scarcely available natural product. Since the producible amount of substance is therefore no longer restricted by low fermentation yields, extensive in vivo studies become possible for the first time. Based on this finding, further investigations on structure-activity relationships were undertaken by variation of the halogen atom, which showed that exchange or omission of the chloro substituent led to significantly lower binding affinities. Furthermore, it was found that elongation of the crucial and characteristic aliphatic side chain at C-10 also increased the IC50 value in the biological assays of interest.
Addresses
  • Department of Chemistry, Johannes Gutenberg-University, Duesbergweg 10-14, 55128 Mainz, Germany. opatz@uni-mainz.de.
Autoren
  • Carina Weber
  • Nina Vierengel
  • Thorsten Walter
  • Torsten Behrendt
  • Tobias Lucas
  • Gerhard Erkel
  • Till Opatz
DOI
10.1039/d0ob00958j
eISSN
1477-0539
Externe Identifier
  • PubMed Identifier: 32691816
Funding acknowledgements
  • Deutsche Forschungsgemeinschaft: Op90/13-1
  • Deutsche Forschungsgemeinschaft: Er176/12-1
Open access
false
ISSN
1477-0520
Ausgabe der Veröffentlichung
30
Zeitschrift
Organic & biomolecular chemistry
Schlüsselwörter
  • Macrocyclic Compounds
Sprache
eng
Medium
Print
Paginierung
5906 - 5917
Datum der Veröffentlichung
2020
Status
Published
Datum der Datenerfassung
2020
Titel
Total synthesis and biological evaluation of seven new anti-inflammatory oxacyclododecindione-type macrolactones.
Sub types
  • Research Support, Non-U.S. Gov't
  • Journal Article
Ausgabe der Zeitschrift
18

Datenquelle: Europe PubMed Central

Abstract
Through variation of our previously published total synthesis of two highly active anti-inflammatory macrolactones from the oxacyclododecindione family (J. Tauber, M. Rohr, T. Walter, G. Erkel and T. Opatz, Org. Biomol. Chem., 2015, 13, 7813-7821), seven new representatives of this compound class were prepared. Substitution of the 14-hydroxy group in oxacyclododecindione with a methyl substituent provided a readily accessible non-natural analogue which has similar pharmacological properties to the scarcely available natural product. Since the producible amount of substance is therefore no longer restricted by low fermentation yields, extensive in vivo studies become possible for the first time. Based on this finding, further investigations on structure-activity relationships were undertaken by variation of the halogen atom, which showed that exchange or omission of the chloro substituent led to significantly lower binding affinities. Furthermore, it was found that elongation of the crucial and characteristic aliphatic side chain at C-10 also increased the IC50 value in the biological assays of interest.
Autoren
  • Carina Weber
  • Nina Vierengel
  • Thorsten Walter
  • Torsten Behrendt
  • Tobias Lucas
  • Gerhard Erkel
  • Till Opatz
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/32691816
DOI
10.1039/d0ob00958j
eISSN
1477-0539
Ausgabe der Veröffentlichung
30
Zeitschrift
Org Biomol Chem
Schlüsselwörter
  • Macrocyclic Compounds
Sprache
eng
Country
England
Paginierung
5906 - 5917
Datum der Veröffentlichung
2020
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2022
Titel
Total synthesis and biological evaluation of seven new anti-inflammatory oxacyclododecindione-type macrolactones.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
18

Datenquelle: PubMed

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