Chitin synthase 2 inhibitory activity of O-methyl pisiferic acid and 8,20-dihydroxy-9(11),13-abietadien-12-one, isolated from Chamaecyparis pisifera.
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.
Kang
Tae Hoon
TH
Korea Research Institute of Bioscience and Biotechnology, PO Box 115, Yusung, Daejeon 305-806, Korea.
Hwang
Eui Il
EI
Yun
Bong Sik
BS
Shin
Chul Soo
CS
Kim
Sung Uk
SU
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
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