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1. Bioorg Med Chem. 2012 Mar 3. [Epub ahead of print]

Synthesis and biological evaluation of bifendate-chalcone hybrids as a new class
of potential P-glycoprotein inhibitors.

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

State Key Laboratory of Natural Medicines, China Pharmaceutical University,
Nanjing 210009, PR China; Center of Drug Discovery, China Pharmaceutical
University, Nanjing 210009, PR China.

Overexpression of P-glycoprotein (P-gp) is one of the major problems to
successful cancer chemotherapy. To find novel effective P-gp inhibitors, a series
of bifendate-chalcone hybrids were synthesized and evaluated. Among them, the
most active compound 8g had little intrinsic cytotoxicity (IC(50)>200μM), and
could increase accumulation of Rhodamine 123 in K562/A02 cells more potently than
bifendate and verapamil (VRP) by inhibiting P-gp efflux function. And 8g
displayed potent chemo-sensitizing effect and persisted for much longer time
(>24h) compared with VRP (<6h). In addition, 8g, unlike VRP, showed no
stimulation on the P-gp ATPase activity, suggesting it is not a P-gp substrate.
Therefore, 8g may represent a promising lead to develop MDR reversal agents for
cancer chemotherapy.

Copyright © 2012 Elsevier Ltd. All rights reserved.

PMID: 22429509 [PubMed - as supplied by publisher]