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Identification of a new antifungal compound inhibiting fatty acid biosynthesis

July 11, 2023

Expected as a new treatment for a global threat, fungal infection

The international collaborative research group, including the researchers at the RIKEN CSRS and the University of Toronto, identified a new compound that shows a fungicidal action by binding to fatty acid synthase to inhibit its function.

Fungal infection has become a serious global public health issue particularly because of the increasing number of multidrug-resistant strains against the existing drugs. Therefore, the development of new antifungal agents is in great demand.

In this study, the international research group screened the RIKEN Natural Product Depository (NPDepo) chemical library for compounds with antifungal activity against four World Health Organization (WHO) critical priority human fungal pathogens to identify a compound NPD6433. Genetic and biochemical analyses revealed that NPD6433 binds to a fatty acid synthase Fas1 to inhibit its enzymatic activity. In addition, they elucidated that NPD6433 kills a fungus in the genera Candida, Candida albicans (C. albicans), and the nematodes infected by C. albicans treated with NPD6433 live longer than those not treated with the compound.

The findings of this study would contribute to the development of promising agents against fungal infections threatening the world, including candidiasis and cryptococcosis.

Original article
Cell Chemical Biology doi: 10.1016/j.chembiol.2023.06.005
K. R. Iyer, S. C. Li, N. M. Revie, J. W. Lou, D. Duncan, S. Fallah, H. Sanchez, I. Skulska, M. M. Ušaj, H. Safizadeh, B. Larsen, C. Wong, A. Aman, T. Kiyota, M. Yoshimura, H. Kimura, H. Hirano, M. Yoshida, H.Osada, A.-C. Gingras, D. R. Andes, R. S. Shapiro, N. Robbins, M. T. Mazhab-Jafari, L. Whitesell, Y. Yashiroda, C. Boone, L. Cowen,
"Identification of triazenyl indoles as inhibitors of fungal fatty acid biosynthesis with broad-spectrum activity".
Contact
Yoko Yashiroda
Deputy Team Leader
Molecular Ligand Target Research Team