Psorospermin structural requirements for P-glycoprotein resistance reversal

Psorospermin structural requirements for P-glycoprotein resistance reversal.

Resistance to chemotherapy reduces its effectiveness, resulting in increased mortality. Psorospermin, a natural product, is a topoisomerase II-directed DNA alkylating agent active against multidrug-resistant (MDR) cell lines, including multiple myeloma. In this study, the mechanism of the P-glycoprotein (P-gp) modulation activity of psorospermin and that of its associated pharmacophore were exa...

Effects of nonionic detergents on P-glycoprotein drug binding and reversal of multidrug resistance.

Multidrug-resistant cells are thought to maintain low intracellular cytotoxic drug concentration though the active efflux of drugs across the cell membrane. It is presently believed that P-glycoprotein mediates this energy-dependent drug efflux by interacting directly with various lipophilic compounds. In this report, we have used [3H]azidopine in a photoaffinity labeling assay to study the eff...

Imaging reversal of multidrug resistance in living mice with bioluminescence: MDR1 P-glycoprotein transports coelenterazine.

Coelenterazine is widely distributed among marine organisms, producing bioluminescence by calcium-insensitive oxidation mediated by Renilla luciferase (Rluc) and calcium-dependent oxidation mediated by the photoprotein aequorin. Despite its abundance in nature and wide use of both proteins as reporters of gene expression and signal transduction, little is known about mechanisms of coelenterazin...

Reversal of P-Glycoprotein-Mediated Multidrug Resistance by Terpenoids from Maytenus Species

Reversal of P-glycoprotein-mediated multidrug resistance in vitro by AV200, a new ardeemin derivative.

The activity of AV200, a synthetic ardeemin derivative, in reversing the multidrug resistance phenotype has been investigated. At non-toxic doses, AV200 was able to completely restore vincristine and paclitaxel toxicities and partially restore that of doxorubicin in multidrug-resistant cells. The potency of AV200 as a modulator of the resistance to doxorubicin, vincristine and paclitaxel result...