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Quinoxaline-substituted chalcones as new inhibitors of breast cancer resistance protein ABCG2: polyspecificity at B-ring position.
- Source :
-
Drug design, development and therapy [Drug Des Devel Ther] 2014 May 27; Vol. 8, pp. 609-19. Date of Electronic Publication: 2014 May 27 (Print Publication: 2014). - Publication Year :
- 2014
-
Abstract
- A series of chalcones substituted by a quinoxaline unit at the B-ring were synthesized and tested as inhibitors of breast cancer resistance protein-mediated mitoxantrone efflux. These compounds appeared more efficient than analogs containing other B-ring substituents such as 2-naphthyl or 3,4-methylenedioxyphenyl while an intermediate inhibitory activity was obtained with a 1-naphthyl group. In all cases, two or three methoxy groups had to be present on the phenyl A-ring to produce a maximal inhibition. Molecular modeling indicated both electrostatic and steric positive contributions. A higher potency was observed when the 2-naphthyl or 3,4-methylenedioxyphenyl group was shifted to the A-ring and methoxy substituents were shifted to the phenyl B-ring, indicating preferences among polyspecificity of inhibition.
- Subjects :
- ATP Binding Cassette Transporter, Subfamily G, Member 2
Antineoplastic Agents chemical synthesis
Antineoplastic Agents chemistry
Cells, Cultured
Chalcones chemical synthesis
Chalcones chemistry
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Female
HEK293 Cells
Humans
Models, Molecular
Molecular Structure
Structure-Activity Relationship
ATP-Binding Cassette Transporters antagonists & inhibitors
Antineoplastic Agents pharmacology
Breast Neoplasms drug therapy
Breast Neoplasms metabolism
Chalcones pharmacology
Drug Resistance, Neoplasm drug effects
Neoplasm Proteins antagonists & inhibitors
Quinoxalines chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1177-8881
- Volume :
- 8
- Database :
- MEDLINE
- Journal :
- Drug design, development and therapy
- Publication Type :
- Academic Journal
- Accession number :
- 24920885
- Full Text :
- https://doi.org/10.2147/DDDT.S56625