| Title | 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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| Author | Jatuporn Phaopongthai1, Suthep Wiyakrutta2, Duangdeun Meksuriyen3, Nongluksna Sriubolmas3, and Khanit Suwanborirux1* |
| Address | 1Center of Bioactive Natural Products from Marine Organisms and Endophytic Fungi (BNPME), Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand, 2Department of Microbiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand, 3Department of Biochemistry and Microbiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand |
| Bibliography | Journal of Microbiology, 51(6),821–828, 2013, |
| DOI | 10.1007/s12275-013-3189-3 |
| Key Words | endophytic fungus, Alternaria alternata, Terminalia chebula, altenusin, biphenyl, azole-synergism, anticandidal activity |
| Abstract | 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. |