Bridgehead Modifications of Englerin A Reduce TRPC4 Activity and Intravenous Toxicity but not Cell Growth Inhibition.
Journal
ACS medicinal chemistry letters
ISSN: 1948-5875
Titre abrégé: ACS Med Chem Lett
Pays: United States
ID NLM: 101521073
Informations de publication
Date de publication:
10 Sep 2020
10 Sep 2020
Historique:
received:
13
04
2020
accepted:
03
08
2020
entrez:
18
9
2020
pubmed:
19
9
2020
medline:
19
9
2020
Statut:
epublish
Résumé
Modifications at the bridgehead position of englerin A were made to explore the effects of variation at this site on the molecule for biological activity, as judged by the NCI 60 screen, in which englerin A is highly potent and selective for renal cancer cells. Replacement of the isopropyl group by other, larger substituents yielded compounds which displayed excellent selectivity and potency comparable to the natural product. Selected compounds were also evaluated for their effect on the ion channel TRPC4 as well as for intravenous toxicity in mice, and these had lower potency in both assays compared to englerin A.
Identifiants
pubmed: 32944138
doi: 10.1021/acsmedchemlett.0c00186
pmc: PMC7488277
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1711-1716Subventions
Organisme : NIH HHS
ID : S10 OD016267
Pays : United States
Organisme : NIGMS NIH HHS
ID : P30 GM110758
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR026962
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA163287
Pays : United States
Organisme : Medical Research Council
ID : MC_PC_17165
Pays : United Kingdom
Organisme : Intramural NIH HHS
ID : ZIA BC011470
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA BC010547
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM104316
Pays : United States
Informations de copyright
Copyright © 2020 American Chemical Society.
Déclaration de conflit d'intérêts
The authors declare no competing financial interest.
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