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.
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