Mycobiology

The Korean Society of Mycology (한국균학회)
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In Vitro Antifungal Activity and Mode of Action of 2',4'-Dihydroxychalcone against Aspergillus fumigatus

  • Seo, Young Ho (College of Pharmacy, Keimyung University) ;
  • Kim, Sung-Su (Department of Biomedical Laboratory Science, Daejeon University) ;
  • Shin, Kwang-Soo (Division of Life Sciences, Daejeon University)
  • Received : 2015.03.04
  • Accepted : 2015.04.08
  • Published : 2015.06.30
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Abstract

2',4'-Dihydroxychalcone (2',4'-DHC) was identified from a heat shock protein 90 (Hsp90)-targeting library as a compound with Hsp90 inhibitory and antifungal effects. In the presence of 2',4'-DHC ($8{\mu}g/mL$), radial growth of Aspergillus fumigatus was inhibited 20% compared to the control, and green pigmentation was completely blocked. The expression of the conidiation-associated genes abaA, brlA, and wetA was significantly decreased (approximately 3- to 5-fold) by treatment with 2',4'-DHC. The expression of calcineurin signaling components, cnaA and crzA, was also significantly reduced. The inhibitory effects of 2',4'-DHC on metabolic activity and mycelial growth were significantly enhanced by combination treatment with itraconazole and caspofungin. Docking studies indicated that 2',4'-DHC bind to the ATPase domain of Hsp90. These results suggest that 2',4'-DHC act as an Hsp90-calcinurin pathway inhibitor.

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References

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