Pure Appl. Chem., 2007, Vol. 79, No. 4, pp. 603-614
doi:10.1351/pac200779040603
Discovery of micafungin (FK463): A novel antifungal drug derived from a natural product lead*
Akihiko Fujie
Fermentation Research Laboratories, Astellas Pharma Inc., 5-2-6 Tokodai, Tsukuba, Ibaraki 300-2698, Japan
Abstract:
FR901379, which is a novel, water-soluble, echinocandin-like lipopeptide, was isolated from a microbial culture broth. It showed potent in vivo antifungal activity against Candida albicans and inhibits the synthesis of 1,3-β-glucan. However, this compound had hemolytic activity and was also less active against Aspergillus fumigatus. To overcome these shortcomings, we synthesized FR131535 bearing an octyloxybenzoyl acyl side chain instead of a fatty acid. FR131535 retained the original activity displayed by FR901379, acquired potent anti-Aspergillus activity, and its hemolytic activity was significantly reduced. Further extensive chemical modification of FR901379 has led to the discovery of micafungin (FK463), which is effective against Candida and Aspergillus spp. Micafungin has been marketed in Japan and the United States as a candin-class parenteral antifungal agent for life-threatening mycoses.
Keywords: antifungal drugs; echinocandin; FK463; FR901379; micafungin.
*Pure Appl. Chem. 79, 467-823 (2007) pp. 467-823. An issue of reviews and research papers based on lectures presented at the 25th International Symposium on Chemistry of Natural Products (ISCNP-25) and 5th International Conference on Biodiversity (ICOB-5), held jointly in Kyoto, Japan, 23-28 July 2006, on the theme of natural products.
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