| RRC ID |
51739
|
| 著者 |
Miyata K, Nakagawa Y, Kimura Y, Ueda K, Akamatsu M.
|
| タイトル |
Structure-activity relationships of dibenzoylhydrazines for the inhibition of P-glycoprotein-mediated quinidine transport.
|
| ジャーナル |
Bioorg Med Chem
|
| Abstract |
We previously demonstrated that dibenzoylhydrazines (DBHs) are not only P-glycoprotein (P-gp) substrates, but also inhibitors. In the present study, we evaluated the inhibition of P-gp-mediated quinidine transport by two series of DBHs and performed a classical QSAR analysis and docking simulation in order to investigate the mechanisms underlying P-gp substrate/inhibitor recognition. The results of the QSAR analysis identified the hydrophobic factor as the most important for inhibitory activities, while electronic and steric effects also influenced the activities. The different substituent effects observed in each series suggested the different binding modes of each series of DBHs, which was supported by the results of the docking simulation.
|
| 巻・号 |
24(14)
|
| ページ |
3184-91
|
| 公開日 |
2016-7-15
|
| DOI |
10.1016/j.bmc.2016.05.039
|
| PII |
S0968-0896(16)30370-4
|
| PMID |
27262425
|
| MeSH |
ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors*
ATP Binding Cassette Transporter, Subfamily B, Member 1 / physiology
Animals
Biological Transport / drug effects*
Humans
Hydrazines / chemistry*
Hydrazines / pharmacology*
Hydrophobic and Hydrophilic Interactions
LLC-PK1 Cells
Molecular Docking Simulation
Quantitative Structure-Activity Relationship
Quinidine / metabolism*
Swine
|
| IF |
3.073
|
| 引用数 |
5
|
| リソース情報 |
| ヒト・動物細胞 |
LLC-GA5-CoL150(RCB0871) |
