摘要：1,3-β- D -Glucan synthase, which synthesizes a main component of fungal cell wall, is one of the promising targets for antifungal agents. In order to identify novel chemical classes of 1,3-β- D -glucan synthase inhibitors, we screened a chemical library monitoring inhibition of the Candida albicans 1,3-β- D -glucan synthase activity. The piperazine propanol derivative GSI578 [(2,6-difluoro-phenyl)-carbamic acid 3-(4-benzothiazol-2-yl-piperazine-1-yl)-propyl ester] was identified as a potent inhibitor against 1,3-β- D -glucan synthase with an IC50 value of 0.16 μ M . GSI578 exhibited in vitro antifungal activity against pathogenic fungi including C. albicans and Aspergillus fumigatus . Temperature-sensitive mutations of the FKS1 gene in the Δ fks2 background of Saccharomyces cerevisiae , where FKS1 and FKS2 encode putative catalytic subunits of 1,3-β- D -glucan synthase, altered sensitivity to GSI578. This suggests that the antifungal activity of the piperazine propanol derivative has an effect on 1,3-β- D -glucan synthase inhibition. Results of our initial evaluation suggest that the piperazine propanol derivative is a novel chemical structure of the class of antifungals which inhibit fungal cell growth by inhibiting fungal 1,3-β- D -glucan synthase.
关键词：cell wall;piperazine propanol;1,3-β- D -glucan synthase;antifungal
