title: Chitin synthase 2 inhibitory activity of O-methyl pisiferic acid and 8,20-dihydroxy-9(11),13-abietadien-12-one, isolated from Chamaecyparis pisifera.
abstract: 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 microM, respectively. Especially, O-methyl pisiferic acid showed 15.3-fold stronger inhibitory activity than polyoxin D (IC50=88.6 microM), 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 (Ki=5 microM). 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 microM, 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.
authors: Korea Research Institute of Bioscience and Biotechnology, PO Box 115, Yusung, Daejeon 305-806, Korea.
authors: Tae Hoon
authors: TH
authors: Kang
authors: Eui Il
authors: EI
authors: Hwang
authors: Bong Sik
authors: BS
authors: Yun
authors: Chul Soo
authors: CS
authors: Shin
authors: Sung Uk
authors: SU
authors: Kim
mesh_terms: D045784:Abietanes / Q000302:isolation & purification / Q000494:pharmacology*; D000935:Antifungal Agents / Q000302:isolation & purification / Q000494:pharmacology*; D029780:Chamaecyparis / Q000737:chemistry*; D002687:Chitin Synthase / Q000037:antagonists & inhibitors*; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D005658:Fungi / Q000187:drug effects; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008566:Membranes / Q000187:drug effects / Q000201:enzymology; D008826:Microbial Sensitivity Tests; D018515:Plant Leaves / Q000737:chemistry; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: C528669:8,20-dihydroxy-9(11),13-abietadien-12-one; D045784:Abietanes; D000935:Antifungal Agents; D004791:Enzyme Inhibitors; C528670:O-methyl pisiferic acid; D002687:Chitin Synthase; C400821:chitin synthase 2