title: In Vitro Antifungal Activity and Mode of Action of 2',4'-Dihydroxychalcone against Aspergillus fumigatus.
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.
authors.affiliation: College of Pharmacy, Keimyung University, Daegu 704-701, Korea.
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Seo
authors.affiliation: Department of Biomedical Laboratory Science, Daejeon University, Daejeon 300-716, Korea.
authors.forename: Sung-Su
authors.initials: SS
authors.lastname: Kim
authors.affiliation: Division of Life Sciences, Daejeon University, Daejeon 300-716, Korea.
authors.forename: Kwang-Soo
authors.initials: KS
authors.lastname: Shin
keywords: 2',4'-Dihydroxychalcone; Antifungal activity; Aspergillus fumigatus; Hsp90 inhibitor