Isolation of Candida albicans chitin synthase 1 inhibitor from Streptomyces sp. A6705 and its characterization

Abstract

In the course of searching for potent chitin synthase 1 inhibitors from natural resources, Streptomyces sp. A6705 was found to exhibit potent inhibitory activity against the chitin synthase 1 from C. albicans (CaCHS1p). As a result, the inhibitor was isolated and identified using a series of chromatographies. Through chemical analyses with UV spectrophotometry, MS spectrometry, and various NMR techniques, the inhibitor was identified as N,N-bis(2-phenylethyl)urea. The compound exhibited strong inhibitory activity against the chitin synthase 1 from C. albicans with an IC50 of 14 μg/ml, representing a similar inhibitory activity to that of the well-known chitin synthase inhibitor, polyoxin D (IC50; 15 μg/ml). However, the compound showed no inhibitory activity against the chitin synthase 2 of Saccharomyces cerevisiae up to 280 μg/ml, which is structurally and functionally analogous to CaCHS1p. In addition, the compound exhibited weak antifungal activities against Cryptococcus neoformans and Rhizoctonis solani.