Research Support, Non-U.S. Gov't
- Azole-synergistic Anti-Candidal Activity of Altenusin, a Biphenyl Metabolite of the Endophytic Fungus Alternaria alternata Isolated from Terminalia chebula Retz.
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Jatuporn Phaopongthai , Suthep Wiyakrutta , Duangdeun Meksuriyen , Nongluksna Sriubolmas , Khanit Suwanborirux
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J. Microbiol. 2013;51(6):821-828. Published online December 19, 2013
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DOI: https://doi.org/10.1007/s12275-013-3189-3
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Abstract
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In this study, a tropical endophytic fungus, Alternaria alternata
Tche-153 was isolated from a Thai medicinal plant
Terminalia chebula Rezt. The ethyl acetate extract prepared
from the fermentation broth exhibited significant ketoconazole-
synergistic activity against Candida albicans. Bioassaydirected
fractionation of the ethyl acetate extract led to the
isolation of altenusin (1), isoochracinic acid (2), and altenuic
acid (3) together with 2,5-dimethyl-7-hydroxychromone
(4). Using the disc diffusion method and the microdilution
chequerboard technique, only altenusin (1) in combination
with each of three azole drugs, ketoconazole, fluconazole or
itraconazole at their low sub-inhibitory concentrations exhibited
potent synergistic activity against C. albicans with the
fractional inhibitory concentration index range of 0.078 to
0.188. This first discovery of altenusin (1) as a new azole-synergistic
prototype possessing a biphenyl structure is of significance
for further development of new azole-synergists
to treat invasive candidiasis.
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