Discovery of Flavonoids as Novel Inhibitors of ATP Citrate Lyase: Structure-Activity Relationship and Inhibition Profiles.
ACLY inhibitor
flavonoid
herbacetin
structure–activity relationship
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
15 Sep 2022
15 Sep 2022
Historique:
received:
16
08
2022
revised:
05
09
2022
accepted:
10
09
2022
entrez:
23
9
2022
pubmed:
24
9
2022
medline:
28
9
2022
Statut:
epublish
Résumé
ATP citrate lyase (ACLY) is a key enzyme in glucolipid metabolism and its aberrantly high expression is closely associated with various cancers, hyperlipemia and atherosclerotic cardiovascular diseases. Prospects of ACLY inhibitors as treatments of these diseases are excellent. To date, flavonoids have not been extensively reported as ACLY inhibitors. In our study, 138 flavonoids were screened and 21 of them were subjected to concentration-response curves. A remarkable structure-activity relationship (SAR) trend was found: ortho-dihydroxyphenyl and a conjugated system maintained by a pyrone ring were critical for inhibitory activity. Among these flavonoids, herbacetin had a typical structure and showed a non-aggregated state in solution and a high inhibition potency (IC
Identifiants
pubmed: 36142671
pii: ijms231810747
doi: 10.3390/ijms231810747
pmc: PMC9504748
pii:
doi:
Substances chimiques
Flavonoids
0
Ligands
0
Pyrones
0
ATP Citrate (pro-S)-Lyase
EC 2.3.3.8
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Project of National Natural Science Foundation of China
ID : 82173962
Organisme : innovation program of science and research
ID : DICP I202018
Organisme : Jiangxi Province
ID : Double Thousand Plan
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