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A candidate inhibitor of filamentous fungal protein kinase C (PKC), Z-705, was identified byin silico screening. A screening system to evaluate the effects of fungal PKC inhibitors was constructed inSaccharomyces cerevisiae . Using this system, we found that Z-705 is highly selective for filamentous fungal PKC in comparison withS. cerevisiae PKC. Analysis of theAGS1 mRNA level, which is regulated by Mps1p mitogen-activated protein kinase (MAPK) via PKC, in the rice blast fungusMagnaporthe grisea revealed that Z-705 had a PKC inhibitory effect comparable to that of staurosporine. Micafungin induced hyphal melanization inM. grisea , and this melanization, which is required for pathogenicity ofM. grisea , was inhibited by PKC inhibition by both Z-705 and staurosporine. The mRNA levels of4HNR ,3HNR , andSCD1 , which are essential for melanization inM. grisea , were suppressed by both PKC inhibitors.

Novel Antifungal Compound Z-705 Specifically Inhibits Protein Kinase C of Filamentous Fungi