2. Academic Validation
  3. Optimization and Evaluation of Novel Antifungal Agents for the Treatment of Fungal Infection

Optimization and Evaluation of Novel Antifungal Agents for the Treatment of Fungal Infection

  • J Med Chem. 2021 Nov 11;64(21):15912-15935. doi: 10.1021/acs.jmedchem.1c01299.
Ji Won Choi 1,  Kyung-Tae Lee 2,  Siwon Kim 1 3,  Ye Rim Lee 1,  Hyeon Ji Kim 1,  Kyung Jin Seo 2,  Myung Ha Lee 2,  Seul Ki Yeon 1,  Bo Ko Jang 4,  Sun Jun Park 1 3,  Hyeon Jeong Kim 1 2,  Jong-Hyun Park 1 3,  Dahee Kim 4,  Dong-Gi Lee 4,  Eunji Cheong 2,  Jong-Seung Lee 4,  Yong-Sun Bahn 2,  Ki Duk Park 1 3
Affiliations

Affiliations

  • 1 Convergence Research Center for Diagnosis, Treatment & Care System of Dementia, Korea Institute of Science & Technology (KIST), Seoul 02792, Republic of Korea.
  • 2 Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea.
  • 3 Division of Bio-Med Science & Technology, KIST School, Korea University of Science and Technology, Seoul 02792, Republic of Korea.
  • 4 AmtixBio Co., Ltd., Hanam-si, Gyeonggi-do 12925, Republic of Korea.
PMID: 34662122 DOI: 10.1021/acs.jmedchem.1c01299
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.

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