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A novel sesquiterpene furan compound CJ-01 was isolated from the methanol extract of the whole plant of Chloranthus japonicus SIEB. by monitoring the inhibitory activity of chitin synthase 2 from Saccharomyces cerevisiae. Based on spectroscopic analysis, the structure of compound CJ-01 was determined as 3,4,8a-trimethyl-4a,7,8,8a-tetrahydro-4a-naphto[2,3-b]furan-9-one. The compound inhibited chitin synthase 2 of Saccharomyces cerevisiae in a dose-dependent manner with an IC50 of 39.6 microg/ml, whereas it exhibited no inhibitory activities against chitin synthase 1 and 3 of S. cerevisiae up to 280 microg/ml. CJ-01 has 1.7-fold stronger inhibitory activity than polyoxin D (IC50=70 microg/ml), a well-known chitin synthase inhibitor. These results indicate that the compound is a specific inhibitor of chitin synthase 2 from S. cerevisiae. In addition, CJ-01 showed antifungal activities against various human and phytopathogenic fungi. Therefore, the compound might be an interesting lead to develop effective antifungal agents.

In the course of search for potent chitin synthase inhibitors from natural resources, a novel chitin synthases inhibitor, 2'-benzoyloxycinnamaldehyde (2'-BCA) (I), was isolated from the aerial parts of Pleuropterus ciliinervis NAKAI. 2'-BCA inhibited chitin synthase 1 and 2 of Saccharomyces cerevisiae with the IC50s of 54.9 and 70.8 microg/ml, respectively, whereas it exhibited no inhibitory activity for chitin synthase 3 up to 280 microg/ml. Its derivatives, 2'-chloro- (V) and 2(-bromo-cinnamaldehyde (VI), each showed 1.9 and 2.7-fold stronger inhibitory activities than 2'-BCA, with the IC50s of 37.2 and 26.6 microg/ml, respectively. Especially, the IC50 of compound VI against chitin synthase 2 represented 1.7-fold more potent inhibitory activity than polyoxin D, a well-known chitin synthase inhibitor. Furthermore, compounds V and VI showed potent antifungal activities against various fungi including human pathogenic fungi, with a particularly strong inhibitory activity against Cryptococcus neoformans (MIC = 16 microg/ml). Although the chemical synthesis of this compound has been reported, the present study is the first report to describe the isolation of 2'-BCA from natural resources and chitin synthases inhibitory activities of its derivatives. These results suggested that 2'-BCA and its derivatives can potentially serve as useful lead compounds for development of antifungal agents.

Three new guaiane type sesquiterpenes were isolated from the methanolic extract of the fruits of Torilis japonica together with a known compound, torilin (1). Their structures were established as 11-acetoxy-8-isobutyryl-4-guaien-3-one (2), 11-acetoxy-8-methacrylyl-4-guaien-3-one (3), and 11-acetoxy-8-propionyl-4-guaien-3-one (4) by spectroscopic methods. These compounds inhibited lipopolysaccharide (LPS)-induced nitric oxide production in murine macrophages RAW 264.7 cells.