Development of Carbazole Derivatives Compounds against Candida albicans: Candidates to Prevent Hyphal Formation via the Ras1-MAPK Pathway
- Authors
- Park, Young-Kwang; Shin, Jisoo; Lee, Hee-Yoon; Kim, Hag-Dong; Kim, Joon
- Issue Date
- Sep-2021
- Publisher
- MDPI
- Keywords
- Candida albicans; MAPK pathway; Ras1; biofilm formation; candidiasis; drug development; drug resistance; fungi; morphogenesis; pathogenicity
- Citation
- JOURNAL OF FUNGI, v.7, no.9
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF FUNGI
- Volume
- 7
- Number
- 9
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/136757
- DOI
- 10.3390/jof7090688
- ISSN
- 2309-608X
- Abstract
- Morphogenesis contributes to the virulence of the opportunistic human fungal pathogen Candida albicans. Ras1-MAPK pathways play a critical role in the virulence of C. albicans by regulating cell growth, morphogenesis, and biofilm formation. Ume6 acts as a transcription factor, and Nrg1 is a transcriptional repressor for the expression of hyphal-specific genes in morphogenesis. Azoles or echinocandin drugs have been extensively prescribed for C. albicans infections, which has led to the development of drug-resistant strains. Therefore, it is necessary to develop new molecules to effectively treat fungal infections. Here, we showed that Molecule B and Molecule C, which contained a carbazole structure, attenuated the pathogenicity of C. albicans through inhibition of the Ras1/MAPK pathway. We found that Molecule B and Molecule C inhibit morphogenesis through repressing protein and RNA levels of Ras/MAPK-related genes, including UME6 and NRG1. Furthermore, we determined the antifungal effects of Molecule B and Molecule C in vivo using a candidiasis murine model. We anticipate our findings are that Molecule B and Molecule C, which inhibits the Ras1/MAPK pathway, are promising compounds for the development of new antifungal agents for the treatment of systemic candidiasis and possibly for other fungal diseases.
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