Optimization and Evaluation of Novel Antifungal Agents for the Treatment of Fungal Infection
- Ji Won Choi
Ji Won ChoiConvergence Research Center for Diagnosis, Treatment & Care System of Dementia, Korea Institute of Science & Technology (KIST), Seoul 02792, Republic of KoreaMore by Ji Won Choi
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- Kyung-Tae Lee
Kyung-Tae LeeDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of KoreaMore by Kyung-Tae Lee
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- Siwon Kim
Siwon KimConvergence Research Center for Diagnosis, Treatment & Care System of Dementia, Korea Institute of Science & Technology (KIST), Seoul 02792, Republic of KoreaDivision of Bio-Med Science & Technology, KIST School, Korea University of Science and Technology, Seoul 02792, Republic of KoreaMore by Siwon Kim
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- Ye Rim Lee
Ye Rim LeeConvergence Research Center for Diagnosis, Treatment & Care System of Dementia, Korea Institute of Science & Technology (KIST), Seoul 02792, Republic of KoreaMore by Ye Rim Lee
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- Hyeon Ji Kim
Hyeon Ji KimConvergence Research Center for Diagnosis, Treatment & Care System of Dementia, Korea Institute of Science & Technology (KIST), Seoul 02792, Republic of KoreaMore by Hyeon Ji Kim
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- Kyung Jin Seo
Kyung Jin SeoDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of KoreaMore by Kyung Jin Seo
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- Myung Ha Lee
Myung Ha LeeDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of KoreaMore by Myung Ha Lee
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- Seul Ki Yeon
Seul Ki YeonConvergence Research Center for Diagnosis, Treatment & Care System of Dementia, Korea Institute of Science & Technology (KIST), Seoul 02792, Republic of KoreaMore by Seul Ki Yeon
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- Bo Ko Jang
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- Sun Jun Park
Sun Jun ParkConvergence Research Center for Diagnosis, Treatment & Care System of Dementia, Korea Institute of Science & Technology (KIST), Seoul 02792, Republic of KoreaDivision of Bio-Med Science & Technology, KIST School, Korea University of Science and Technology, Seoul 02792, Republic of KoreaMore by Sun Jun Park
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- Hyeon Jeong Kim
Hyeon Jeong KimConvergence Research Center for Diagnosis, Treatment & Care System of Dementia, Korea Institute of Science & Technology (KIST), Seoul 02792, Republic of KoreaDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of KoreaMore by Hyeon Jeong Kim
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- Jong-Hyun Park
Jong-Hyun ParkConvergence Research Center for Diagnosis, Treatment & Care System of Dementia, Korea Institute of Science & Technology (KIST), Seoul 02792, Republic of KoreaDivision of Bio-Med Science & Technology, KIST School, Korea University of Science and Technology, Seoul 02792, Republic of KoreaMore by Jong-Hyun Park
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- Dahee Kim
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- Dong-Gi Lee
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- Eunji Cheong
Eunji CheongDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of KoreaMore by Eunji Cheong
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- Jong-Seung Lee*
Jong-Seung Lee*Email: [email protected]AmtixBio Co., Ltd., Hanam-si, Gyeonggi-do 12925, Republic of KoreaMore by Jong-Seung Lee
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- Yong-Sun Bahn*
Yong-Sun Bahn*Email: [email protected]Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of KoreaMore by Yong-Sun Bahn
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- Ki Duk Park*
Ki Duk Park*Email: [email protected]Convergence Research Center for Diagnosis, Treatment & Care System of Dementia, Korea Institute of Science & Technology (KIST), Seoul 02792, Republic of KoreaDivision of Bio-Med Science & Technology, KIST School, Korea University of Science and Technology, Seoul 02792, Republic of KoreaMore by Ki Duk Park
Abstract
Due to the increased morbidity and mortality by fungal infections and the emergence of severe antifungal resistance, there is an urgent need for new antifungal agents. Here, we screened for antifungal activity in our in-house library through the minimum inhibitory concentration test and derived two hit compounds with moderate antifungal activities. The hit compounds’ antifungal activities and drug-like properties were optimized by substituting various aryl ring, alkyl chain, and methyl groups. Among the optimized compounds, 22h was the most promising candidate with good drug-like properties and exhibited potent fast-acting fungicidal antifungal effects against various fungal pathogens and synergistic antifungal activities with some known antifungal drugs. Additionally, 22h was further confirmed to disturb fungal cell wall integrity by activating multiple cell wall integrity pathways. Furthermore, 22h exerted significant antifungal efficacy in both the subcutaneous infection mouse model and ex vivo human nail infection model.
Cited By
This article is cited by 3 publications.
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- Kyung-Tae Lee, Dong-Gi Lee, Ji Won Choi, Jong-Hyun Park, Ki Duk Park, Jong-Seung Lee, Yong-Sun Bahn. The novel antifungal agent AB-22 displays in vitro activity against hyphal growth and biofilm formation in Candida albicans and potency for treating systemic candidiasis. Journal of Microbiology 2022, 60 (4) , 438-443. https://doi.org/10.1007/s12275-022-2016-0
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