Total Synthesis and Bioactivity Mapping of Geodiamolide H.
Actin
antitumor agents
natural products
structure-activity relationship
total synthesis
Journal
Chemistry (Weinheim an der Bergstrasse, Germany)
ISSN: 1521-3765
Titre abrégé: Chemistry
Pays: Germany
ID NLM: 9513783
Informations de publication
Date de publication:
11 Aug 2021
11 Aug 2021
Historique:
received:
18
04
2021
pubmed:
26
5
2021
medline:
18
8
2021
entrez:
25
5
2021
Statut:
ppublish
Résumé
The first total synthesis of the actin-stabilizing marine natural product geodiamolide H was achieved. Solid-phase based peptide assembly paired with scalable stereoselective syntheses of polyketide building blocks and an optimized esterification set the stage for investigating the key ring-closing metathesis. Geodiamolide H and synthetic analogues were characterized for their toxicity and for antiproliferative effects in cellulo, by characterising actin polymerization induction in vitro, and by docking on the F-actin target and property computation in silico, for a better understanding of structure-activity relationships (SAR). A non-natural analogue of geodiamolide H was discovered to be most potent in the series, suggesting significant potential for tool compound design.
Identifiants
pubmed: 34032329
doi: 10.1002/chem.202100989
pmc: PMC8453818
doi:
Substances chimiques
Actins
0
Biological Products
0
Depsipeptides
0
geodiamolide H
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
11633-11642Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : SFB 1127/2
Organisme : Deutscher Akademischer Austauschdienst
ID : PhD fellowship
Organisme : Werner-Siemens Stiftung
Informations de copyright
© 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.
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