标题：Chitin Synthase 2 Inhibitory Activity of O-Methyl Pisiferic Acid and 8,20-Dihydroxy-9(11),13-abietadien-12-one, Isolated from Chamaecyparis pisifera
摘要：In the course of search for potent chitin synthase inhibitors from plant extracts, the chitin synthase 2 inhibitors, O -methyl pisiferic acid and 8,20-dihydroxy-9(11),13-abietadien-12-one which have diterpene skeleton, were isolated from the leaves of Chamaecyparis pisifera . These compounds inhibited chitin synthase 2 of Saccharomyces cerevisiae with the IC50 values of 5.8 and 226.4 μ M , respectively. Especially, O -methyl pisiferic acid showed 15.3-fold stronger inhibitory activity than polyoxin D (IC50=88.6 μ M ), a well-known chitin synthase inhibitor. These compounds exhibited weaker inhibitory activities against chitin synthase 1 than chitin synthase 2, whereas it showed no inhibitory activity for chitin synthase 3. The compound exhibited mixed competitive inhibition with respect to UDP- N -acetyl- D -glucosamine as substrate ( K i=5 μ M ). These results indicated that O -methyl pisiferic acid is a specific inhibitor of chitin synthase 2. The compound also inhibited chitin synthase 1 of Candida albicans , which represents analogues to chitin synthase 2 of S. cerevisiae , with an IC50 of 75.6 μ M , which represents 1.8-fold weaker activity than that of polyoxin D. Although O -methyl pisiferic acid has been reported for antibacterial and insecticidal activities, the present study is the first report on its inhibitory activity against chitin synthase 2.
