Synthesis and structure-activity relationship studies of α-naphthoflavone derivatives as CYP1B1 inhibitors.
3D-QSAR
CYP1B1 inhibitors
SARs
α-naphthoflavones
Journal
European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510
Informations de publication
Date de publication:
01 Feb 2020
01 Feb 2020
Historique:
received:
17
08
2019
revised:
28
11
2019
accepted:
30
11
2019
pubmed:
13
12
2019
medline:
11
3
2020
entrez:
13
12
2019
Statut:
ppublish
Résumé
Cytochrome P450 1B1(CYP1B1) has been recognized as an important target for cancer prevention and drug resistance reversal. In order to obtain potent and selective CYP1B1 inhibitors, a series of forty-one α-naphthoflavone (ANF) derivatives were synthesized, characterized, and evaluated for CYP1B1, CYP1A1 and CYP1A2 inhibitory activities. A closure look into the structure-activity relationship for the inhibitory effects on CYP1B1 indicated that modification of the C ring of ANF would decrease the CYP1B1 inhibitory potency, while incorporation of substituent(s) into the different positions of the B ring yielded analogues with varying CYP1B1 inhibitory capacity. Among these derivatives, compounds 9e and 9j were identified as the most potent two selective CYP1B1 inhibitors with IC
Identifiants
pubmed: 31830634
pii: S0223-5234(19)31090-6
doi: 10.1016/j.ejmech.2019.111938
pii:
doi:
Substances chimiques
Benzoflavones
0
Enzyme Inhibitors
0
Recombinant Proteins
0
alpha-naphthoflavone
604-59-1
CYP1B1 protein, human
EC 1.14.14.1
Cytochrome P-450 CYP1B1
EC 1.14.14.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
111938Informations de copyright
Copyright © 2019 Elsevier Masson SAS. All rights reserved.