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

Abstract

Arborcandins A, B, C, D, E and F, which possess potent 1,3-β-glucan synthase inhibitory activity, were isolated from the culture broth of a filamentous fungus, strain SANK 17397. Arborcandins are novel cyclic peptides, that are structurally different from known glucan synthase inhibitors such as echinocandins. The 1,3-β-glucan synthase of Candida albicans and Aspergillus fumigatus were inhibited by arborcandins with IC50 ranging from 0.012 to 3 μg/ml. The apparent Ki value of arborcandin C for C. albicans and A. fumigatus were 0.12 μM and 0.016 μM, respectively. The inhibition against these two 1,3-β-glucan synthases by arborcandin C was noncompetitive. These compounds exhibited potent fungicidal activity against Candida spp. with MIC ranging from 0.25 to 8 μg/ml. The growth of A. fumigatus was suppressed by arborcandins with concentrations ranging from 0.063 to 4 μg/ml.