In Vitro Antifungal Activity and Mode of Action of 2',4'-Dihydroxychalcone against Aspergillus fumigatus

  • Mycobiology. 2015 Jun;43(2):150-6. doi: 10.5941/MYCO.2015.43.2.150.
Young Ho Seo  1 ,  Sung-Su Kim  2 ,  Kwang-Soo Shin  3
Affiliations
  • 1. College of Pharmacy, Keimyung University, Daegu 704-701, Korea.
  • 2. Department of Biomedical Laboratory Science, Daejeon University, Daejeon 300-716, Korea.
  • 3. Division of Life Sciences, Daejeon University, Daejeon 300-716, Korea.
PMID: 26190922 DOI: 10.5941/MYCO.2015.43.2.150
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 µg/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.

Keywords
2',4'-Dihydroxychalcone; Antifungal activity; Aspergillus fumigatus; Hsp90 inhibitor.
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