Arborcandins A, B, C, D, E and F, novel 1,3-beta-glucan synthase inhibitors: Production and biological activity

Arborcandins A, B, C, D, E and F, which possess potent 1,3-beta -glucan syn thase inhibitory activity, were isolated from the culture broth of a filame ntous fungus, strain SANK 17397. Arborcandins are novel cyclic peptides, th at are structurally different from known glucan synthase inhibitors such as echinocandins. The 1,3-beta -glucan synthases of Candida albicans and Aspe rgillus fumigatus were inhibited by arborcandins with IC50 ranging from 0.0 12 to 3 mug/ml. The apparent Ki value of arborcandin C for C. albicans and A. fumigatus were 0.12 muM and 0.016 muM, respectively The inhibition again st these two 1,3-beta -glucan syntheses by arborcandin C was noncompetitive . These compounds exhibited potent fungicidal activity against Candida spp. with MIC ranging from 0.25 to 8 mug/ml. The growth of A. fumigatus was sup pressed by arborcandins with concentrations ranging from 0.063 to 4 mug/ml.