Abstract：
:Invasive fungal infections remain a challenge due to lack of effective antifungal agents and serious drug resistance. Discovery of antifungal agents with novel antifungal mechanism is important and urgent. Previously, we designed the first CYP51/HDAC dual inhibitors with potent activity against resistant Candida albicans infections. To better understand the antifungal spectrum and synergistic mechanism, herein new CYP51/HDAC dual inhibitors were designed which showed potent in vitro and in vivo antifungal activity against C. neoformans and C. tropicalis infections. Antifungal mechanism studies revealed that the CYP51/HDAC dual inhibitors acted by inhibiting various virulence factors of C. tropicalis and C. neoformans and down-regulating resistance-associated genes. This study highlights the potential of CYP51/HDAC dual inhibitors as a promising strategy for the discovery of novel broad-spectrum antifungal agents.
journal_name
Eur J Med Chemjournal_title
European journal of medicinal chemistryauthors
Zhu T,Chen X,Li C,Tu J,Liu N,Xu D,Sheng Cdoi
10.1016/j.ejmech.2021.113524keywords:
["Antifungal","CYP51\/HDAC dual Inhibitors","Candida tropicalis","Cryptococcus neoformans","Virulence factors"]subject
Has Abstractpub_date
2021-10-05 00:00:00pages
113524eissn
0223-5234issn
1768-3254pii
S0223-5234(21)00373-1journal_volume
221pub_type
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