pgp - publications

Predict more pgp - ligand interactions now!


1. Eur J Med Chem. 2012 Feb 25. [Epub ahead of print]

Synthesis and biological evaluation of novel bifendate derivatives bearing
6,7-dihydro-dibenzo[c,e]azepine scaffold as potent P-glycoprotein inhibitors.

Gu X, Ren Z, Tang X, Peng H, Zhao Q, Lai Y, Peng S, Zhang Y.

State Key Laboratory of Natural Medicines, China Pharmaceutical University,
Nanjing 210009, People's Republic of China; Center of Drug Discovery, China
Pharmaceutical University, Nanjing 210009, People's Republic of China.

Overexpression of P-glycoprotein (P-gp) is one of the major problems in
successful treatment of cancers. To find new P-gp inhibitors, a series of
bifendate (DDB) derivatives bearing dibenzo[c,e]azepine scaffold were synthesized
and evaluated. Compound 4i more potently reversed P-gp-mediated multidrug
resistance (MDR) than DDB and verapamil (VRP) by blocking P-gp mediated drug
efflux function and increasing drug accumulation in K562/A02 MDR cells, and
persisted longer chemo-sensitizing effect (>24 h) than VRP (<6 h). Interestingly,
unlike VRP, 4i showed no stimulation on the P-gp ATPase activity, suggesting it
is not a substrate of P-gp. Given the low intrinsic cytotoxicity of 4iin vitro,
it may represent a promising lead for developing therapeutics targeting
P-gp-mediated MDR in combinational cancer chemotherapy.

Copyright © 2012 Elsevier Masson SAS. All rights reserved.

PMID: 22405646 [PubMed - as supplied by publisher]