A first-in-class inhibitor of Hsp110 molecular chaperones of pathogenic fungi

Liqing Hu, Cancan Sun, Justin M. Kidd, Jizhong Han, Xianjun Fang, Hongtao Li, Qingdai Liu, Aaron E. May, Qianbin Li, Lei Zhou () and Qinglian Liu ()
Additional contact information
Liqing Hu: Virginia Commonwealth University
Cancan Sun: Virginia Commonwealth University
Justin M. Kidd: Virginia Commonwealth University
Jizhong Han: Shenzhen Bay Laboratory
Xianjun Fang: Virginia Commonwealth University
Hongtao Li: Virginia Commonwealth University
Qingdai Liu: Tianjin University of Science & Technology
Aaron E. May: Virginia Commonwealth University
Qianbin Li: Central South University
Lei Zhou: Shenzhen Bay Laboratory
Qinglian Liu: Virginia Commonwealth University

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract Proteins of the Hsp110 family are molecular chaperones that play important roles in protein homeostasis in eukaryotes. The pathogenic fungus Candida albicans, which causes infections in humans, has a single Hsp110, termed Msi3. Here, we provide proof-of-principle evidence supporting fungal Hsp110s as targets for the development of new antifungal drugs. We identify a pyrazolo[3,4-b] pyridine derivative, termed HLQ2H (or 2H), that inhibits the biochemical and chaperone activities of Msi3, as well as the growth and viability of C. albicans. Moreover, the fungicidal activity of 2H correlates with its inhibition of in vivo protein folding. We propose 2H and related compounds as promising leads for development of new antifungals and as pharmacological tools for the study of the molecular mechanisms and functions of Hsp110s.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-38220-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38220-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-38220-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().