2. Academic Validation
  3. Discovery of Novel 8-Hydroxyquinoline Derivatives with Potent In Vitro and In Vivo Antifungal Activity

Discovery of Novel 8-Hydroxyquinoline Derivatives with Potent In Vitro and In Vivo Antifungal Activity

  • J Med Chem. 2023 Dec 14;66(23):16364-16376. doi: 10.1021/acs.jmedchem.3c01771.
Liping Li 1,  Hao Wu 1,  Jiayin Wang 1 2,  Zhe Ji 1,  Ting Fang 1,  Hui Lu 1,  Lan Yan 3,  Fuming Shen 1,  Dazhi Zhang 1 3,  Yuanying Jiang 1,  Tingjunhong Ni 1
Affiliations

Affiliations

  • 1 Department of Pharmacy, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, No. 1239 Siping Road, Shanghai 200092, China.
  • 2 School of Pharmacy, Fujian University of Traditional Chinese Medicine, 1 Qiuyang Road, Fuzhou 350112, China.
  • 3 School of Pharmacy, Naval Medical University, PLA, No. 325 Guohe Road, Shanghai 200433, China.
PMID: 37975824 DOI: 10.1021/acs.jmedchem.3c01771
Abstract

Fungal pathogens can cause life-threatening infections, yet current antifungals are inadequate at treating many of these, highlighting the importance of novel drug discovery. Here, we report hit compound L14, a novel 8-hydroxyquinoline derivative with potent and broad-spectrum Antifungal activity. In vitro experiments exhibited that L14 had better activity and lower cytotoxicity than that of clioquinol and showed synergy in combination with fluconazole (FLC). In a Candida albicans-infected murine model, L14 at 2 mg/kg showed better in vivo efficacy than clioquinol at reducing Fungal burden and extending the survival of C. albicans-infected mice. In addition, L14 alone or in combination with FLC had significant inhibitory activity against hypha and biofilm formation. Overall, our data indicated that 8-hydroxyquinoline derivative L14 has favorable pharmacokinetics and acceptable safety profiles and could be further investigated as a promising Antifungal hit compound.

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