Abstract |
As a continuation of previous research, fifteen bifendate derivatives bearing 6,7-dihydro-dibenzo [c,e]azepine scaffold were synthesized and evaluated as P-gp-medicated multidrug resistance (MDR) reversal agents. Biological evaluation indicated that compounds 6k and 9c more potently reversed P-gp-mediated MDR than bifendate and verapamil (VRP) by blocking P-gp mediated drug efflux function and not by decreasing P-gp expression in K562/A02 MDR cells. Interestingly, wound-healing and chamber migration assay showed that 6k and 9c could significantly attenuate the migration of MDA-MB-231 cells. Notably, 6k and 9c could markedly suppress the invasive activity of MDA-MB-231 cells, thus displayed potential anti- metastasis activity. Preliminary mechanism studies indicated that the anti- metastasis activity of 6k and 9c was associated with their inhibitory effect on the activity and expression of MMP-2 and MMP-9. These results, together with the MDR reversal results indicated that compounds 6k and 9c might be promising leads for developing novel anti- cancer agents with P-gp and tumor metastasis inhibitory activities.
|
Authors | Xiaoke Gu, Yanfei Jiang, Yingying Qu, Jing Chen, Dingding Feng, Chenglin Li, Xiaoxing Yin |
Journal | European journal of medicinal chemistry
(Eur J Med Chem)
Vol. 145
Pg. 379-388
(Feb 10 2018)
ISSN: 1768-3254 [Electronic] France |
PMID | 29335204
(Publication Type: Journal Article)
|
Copyright | Copyright © 2018 Elsevier Masson SAS. All rights reserved. |
Chemical References |
- ATP Binding Cassette Transporter, Subfamily B, Member 1
- Antineoplastic Agents
- Azepines
- Biphenyl Compounds
- bifendate
|
Topics |
- ATP Binding Cassette Transporter, Subfamily B, Member 1
(antagonists & inhibitors, metabolism)
- Antineoplastic Agents
(chemical synthesis, chemistry, pharmacology)
- Azepines
(chemistry, pharmacology)
- Biphenyl Compounds
(chemical synthesis, chemistry, pharmacology)
- Cell Line, Tumor
- Dose-Response Relationship, Drug
- Drug Resistance, Multiple
(drug effects)
- Drug Resistance, Neoplasm
(drug effects)
- Drug Screening Assays, Antitumor
- Humans
- K562 Cells
- Molecular Structure
- Neoplasms
(drug therapy, metabolism, pathology)
- Structure-Activity Relationship
|