Inhibition of Chitin Synthase 2 and Antifungal Activity of Lignans from the Stem Bark of Lindera erythrocarpa

Abstract

Potent chitin synthase 2 inhibitors, methyllinderone (1), linderone (2) and kanakugiol (3) were isolated from the stem bark of L. erythrocarpa Makino (Lauraceae). These compounds inhibited chitin synthase 2 with IC₅₀ values of 23.3, 21.4 and 23.8 μg/mL, respectively. Methyllinderone (1) and linderone (2) exhibited no inhibitory activities for chitin synthases 1 and 3 from S. cerevisiae, and chitin synthase 1 from Candida albicans up to the concentration of 280 μg/mL, while kanakugiol (3) exhibited very weak activity against chitin synthase 1 of C. albicans with an IC₅₀ of 160 μg/mL. All of the compounds showed moderate to weak antifungal activities against various pathogenic fungi (MIC: 8 - >128 μg/mL) including Cryptococcus neoformans, Aspergillus fumigatus, and Colletotrichum lagenarium. The results indicate that these compounds are specific inhibitors of chitin synthase 2 and can potentially serve as antifungal agents.

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