Design and synthesis of α-naphthoflavone chimera derivatives able to eliminate cytochrome P450 (CYP)1B1-mediated drug resistance via targeted CYP1B1 degradation.
CYP1B1
Click reaction
PROTACs
Reversal of drug resistance
α-Naphthoflavone-based conjugates
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 Mar 2020
01 Mar 2020
Historique:
received:
15
10
2019
revised:
29
12
2019
accepted:
30
12
2019
pubmed:
17
1
2020
medline:
17
7
2020
entrez:
17
1
2020
Statut:
ppublish
Résumé
Extrahepatic cytochrome P450 1B1 (CYP1B1), which is highly expressed in various tumors, is an attractive and potential target for cancer prevention, therapy, and reversal of drug resistance. CYP1B1 inhibition is the current predominant therapeutic paradigm to treating CYP1B1-mediated malignancy, but therapeutic effect has little success. Herein, we reported CYP1B1 degradation in place of CYP1B1 inhibition for reversing drug resistance toward docetaxel in CYP1B1-overexpressing prostate cancer cell line DU145 using a PROTAC strategy. Replacing chlorine atom of a CYP1B1 selective inhibitor we found previously with ethynyl, we got the resulting α-naphthoflavone derivative 5 which kept strong inhibition against CYP1B1 (IC
Identifiants
pubmed: 31945665
pii: S0223-5234(19)31186-9
doi: 10.1016/j.ejmech.2019.112028
pii:
doi:
Substances chimiques
Benzoflavones
0
Docetaxel
15H5577CQD
Thalidomide
4Z8R6ORS6L
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
112028Informations de copyright
Copyright © 2020 Elsevier Masson SAS. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.