The Cyclic Organosulfur Compound Zwiebelane A from Onion (Allium cepa) Functions as an Enhancer of Polymyxin B in Fungal Vacuole Disruption

Abstract

Zwiebelane A (cis-2,3-dimethyl-5,6-dithiabicyclo[2.1.1]hexane 5-oxide), a natural product of onion bulbs (Allium cepa L.), is found to enhance the potential fungicidal activity of polymyxin B (PMB). As is the case with allicin, an allyl sulfur compound from garlic, zwiebelane A amplifies the disruptive effect of PMB on the vacuole of Saccharomyces cerevisiae, which has been found to represent a target for antifungal agents.

Key words

Allium cepa - Alliaceae - zwiebelane A - polymyxin B - Saccharomyces cerevisiae

References

• 1 Ankri S, Mirelman D. Antimicrobial properties of allicin from garlic.  Microbes Infect. 1999;  1 125-129
• 2 Oommen S, Anto R J, Srinivas G, Karunagaran D. Allicin (from garlic) induces caspase-mediated apoptosis in cancer cells.  Eur J Pharmacol. 2004;  485 97-103
• 3 Coppi A, Cabinan M, Mirelman D, Sinnis P. Antimalarial activity of allicin, a biologically active compound from garlic cloves.  Antimicrob Agents Chemother. 2006;  50 1731-1737
• 4 Ogita A, Fujita K, Taniguchi M, Tanaka T. Enhancement of the fungicidal activity of amphotericin B by allicin, an allyl-sulfur compound from garlic, against the yeast Saccharomyces cerevisiae as a model system.  Planta Med. 2006;  72 1247-1250
• 5 Ogita A, Matsumoto K, Fujita K, Usuki Y, Hatanaka Y, Tanaka T. Synergistic fungicidal activities of amphotericin B and N-methyl-N"-dodecylguanidine: a constituent of polyol macrolide antibiotic niphimycin.  J Antibiot. 2007;  60 27-35
• 6 Ogita A, Fujita K, Tanaka T. Enhancement of the fungicidal activity of amphotericin B by allicin: effects on intracellular ergosterol trafficking.  Planta Med. 2009;  75 222-226
• 7 Borjihan H, Ogita A, Fujita K, Hirasawa E, Tanaka T. The vacuole-targeting fungicidal activity of amphotericin B against the pathogenic fungus Candida albicans and its enhancement by allicin.  J Antibiot. 2009;  62 691-697
• 8 Ogita A, Fujita K, Usuki Y, Tanaka T. Targeted yeast vacuole disruption by polyene antibiotics with a macrocyclic lactone ring.  Int J Antimicrob Agents. 2010;  35 89-92
• 9 Ogita A, Nagao Y, Fujita K, Tanaka T. Amplification of vacuole-targeting fungicidal activity of antibacterial antibiotic polymyxin B by allicin, an allyl sulfur compound from garlic.  J Antibiot. 2007;  60 511-518
• 10 Ogita A, Konishi Y, Borjihan B, Fujita K, Tanaka T. Synergistic fungicidal activities of polymyxin B and ionophores, and their dependence on direct disruptive action of polymyxin B on fungal vacuole.  J Antibiot. 2009;  62 81-87
• 11 Bayer T, Wagner H, Block E, Grisoni S, Zhao S H, Neszmelyi A. Zwiebelanes: novel biologically active 2,3-dimethyl-5,6-dithiabicyclo[2.1.1.]hexane-5-oxides from onion.  J Am Chem Soc. 1989;  111 3085-3086
• 12 Thumm M. Structure and function of the yeast vacuole and its role in autophagy.  Microsc Res Tech. 2000;  51 563-572
• 13 Davis S R. An overview of the antifungal properties of allicin and its breakdown products – the possibility of a safe and effective antifungal prophylactic.  Micoses. 2005;  48 95-100
• 14 Davies H M L, Huby N J S, Cantrell W R, Olive J L. Alpha-hydroxy esters as chiral auxiliaries in asymmetric cyclopropanations by rhodium (II)-stabilized vinylcarbenoids.  J Am Chem Soc. 1993;  115 9468-9479