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)>200 μM), 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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmc.2012.02.050 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Bifendate-chalcone hybrids: a new class of potential dual inhibitors of P-glycoprotein and breast cancer resistance protein.
Biochem Biophys Res Commun
December 2014
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, People's Republic of China. Electronic address:
We previously described bifendate-chalcone hybrids as potent P-glycoprotein inhibitors. In the present work, we determine whether these compounds could reverse breast cancer resistance protein (BCRP, ABCG2)-mediated multidrug resistance using HEK293/BCRP cells which was BCRP-transfected stable HEK293 cells. Results indicated that compounds 8d, 8f, 8g and 8h could significantly enhance mitoxantrone accumulation in HEK293/BCRP cells via inhibiting BCRP drug efflux function.
View Article and Find Full Text PDFSynthesis and biological evaluation of bifendate-chalcone hybrids as a new class of potential P-glycoprotein inhibitors.
Bioorg Med Chem
April 2012
State Key Laboratory of Natural Medicines, 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)>200 μM), and could increase accumulation of Rhodamine 123 in K562/A02 cells more potently than bifendate and verapamil (VRP) by inhibiting P-gp efflux function.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!