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Biological Chemistry

Natural Product Sidesteps Drug Resistance In Yeast

Enzyme inhibitor could lead to new pharmaceuticals

by Stu Borman
January 17, 2011 | APPEARED IN VOLUME 89, ISSUE 3

Oroidin, a natural product isolated from a marine sponge, inhibits an enzyme responsible for multidrug resistance in yeast. It could thus aid the development of antifungal drugs that targeted microorganisms wouldn’t be able to resist and anticancer drugs that sidestep a similar resistance mechanism in tumor cells. An enzyme called Pdr5p is able to help yeast get rid of drugs by pumping them through yeast cell membranes. Its structure and function are similar to those of P-glycoprotein, a multidrug-transport protein in mammalian cells. Antonio Ferreira-Pereira of the Federal University of Rio de Janeiro and coworkers found that an extract from the marine sponge Agelas sventres inhibits Pdr5p, discovered the small molecule oroidin to be the active agent, and characterized the compound (J. Nat. Prod., DOI: 10.1021/np1006247). The agent could lead to antifungal drugs for cells with the multi­drug-resistance phenotype. In addition, it could be used to screen for compounds that inhibit P-glycoprotein and that might be more effective and/or less toxic than current multidrug-resistance-avoiding anti­cancer agents, such as verapamil, tamoxifen, and cyclosporine A.

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