Choi, Ji Won Lee, Kyung-Tae Kim, Siwon Lee, Ye Rim Kim, Hyeon Ji Seo, Kyung Jin Lee, Myung Ha Yeon, Seul Ki Jang, Bo Ko Park, Sun Jun Kim, Hyeon Jeong Park, Jong-Hyun Kim, Dahee Lee, Dong-Gi Cheong, Eunji Lee, Jong-Seung Bahn, Yong-Sun Park, Ki Duk 2024-01-19T13:30:49Z 2024-01-19T13:30:49Z 2022-01-10 2021-11-11 0022-2623 https://pubs.kist.re.kr/handle/201004/116138 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. English American Chemical Society Optimization and Evaluation of Novel Antifungal Agents for the Treatment of Fungal Infection Article 10.1021/acs.jmedchem.1c01299 1 Journal of Medicinal Chemistry, v.64, no.21, pp.15912 - 15935 Journal of Medicinal Chemistry 64 21 15912 15935 N scie scopus 000718382200027 2-s2.0-85118576206 Chemistry, Medicinal Pharmacology & Pharmacy Article CANDIDA-ALBICANS DISEASES SOCIETY CALCINEURIN RESISTANCE MANAGEMENT INHIBITORS INTEGRITY SYNTHASE PATHWAY UPDATE