Polygodial, an antifungal potentiator.
A series of sesquiterpene dialdehydes was isolated from the East African medicinal plants Warburgia stuhlmannii and Warburgia ugandensis (Canellaceae) as antibiotics, particularly against Saccharomyces cerevisiae, Candida utilis, and Sclerotinia libertiana. Among these sesquiterpene dialdehydes, polygodial [1] exhibited the most potent activity. When tested on S. cerevisiae, polygodial proved to be fungicidal rather than fungistatic. When the cells of S. cerevisiae are treated in vitro with polygodial for 10 min, the cell membrane becomes severely damaged, and many vesicles, possibly formed from the fragmented cell membrane, can be observed within the cytoplasm. The observation of cell membrane lesions led us to propose a rather innovative hypothesis: the use of polygodial to facilitate the transmembrane transport of exogenous chemicals into cells. For example, polygodial could be combined with an antibiotic having poor cell membrane permeability in an effort to increase its antibiotic activity by increasing its ability to gain entrance into the cell. We report here that a remarkably enhanced efficacy was obtained when actinomycin D was used in combination with polygodial. We believe polygodial may be acting as an "advance scout," punching holes in the plasma membrane and gaining an entrance into the cell for an antibiotic previously less effective because of problems with cell membrane permeability.
Kubo
I
I
Division of Entomology and Parasitology, College of Natural Resources, University of California, Berkeley 94720.
Taniguchi
M
M
D000935:Antifungal Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D003609:Dactinomycin / Q000494:pharmacology; D004357:Drug Synergism; D008826:Microbial Sensitivity Tests; D010946:Plants, Medicinal / Q000032:analysis*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000648:ultrastructure; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D015003:Yeasts / Q000187:drug effects
D000935:Antifungal Agents; D012717:Sesquiterpenes; D003609:Dactinomycin; C034380:polygodial