Isomerization of bioactive acylhydrazones triggered by light or thiols.
Journal
Nature chemistry
ISSN: 1755-4349
Titre abrégé: Nat Chem
Pays: England
ID NLM: 101499734
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
received:
02
02
2022
accepted:
12
05
2023
medline:
1
9
2023
pubmed:
13
6
2023
entrez:
12
6
2023
Statut:
ppublish
Résumé
The acylhydrazone unit is well represented in screening databases used to find ligands for biological targets, and numerous bioactive acylhydrazones have been reported. However, potential E/Z isomerization of the C=N bond in these compounds is rarely examined when bioactivity is assayed. Here we analysed two ortho-hydroxylated acylhydrazones discovered in a virtual drug screen for modulators of N-methyl-D-aspartate receptors and other bioactive hydroxylated acylhydrazones with structurally defined targets reported in the Protein Data Bank. We found that ionized forms of these compounds, which are populated under laboratory conditions, photoisomerize readily and the isomeric forms have markedly different bioactivity. Furthermore, we show that glutathione, a tripeptide involved with cellular redox balance, catalyses dynamic E⇄Z isomerization of acylhydrazones. The ratio of E to Z isomers in cells is determined by the relative stabilities of the isomers regardless of which isomer was applied. We conclude that E/Z isomerization may be a common feature of the bioactivity observed with acylhydrazones and should be routinely analysed.
Identifiants
pubmed: 37308709
doi: 10.1038/s41557-023-01239-5
pii: 10.1038/s41557-023-01239-5
doi:
Substances chimiques
Sulfhydryl Compounds
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1285-1295Subventions
Organisme : CIHR
ID : FDN-154286
Pays : Canada
Organisme : CIHR
ID : FRN-148463
Pays : Canada
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature Limited.
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