Inhibition of chitin synthase 2 and antifungal activity of lignans from the stem bark of Lindera erythrocarpa.
Potent chitin synthase 2 inhibitors, methyllinderone (1), linderone (2) and kanakugiol (3) were isolated from the stem bark of L. erythrocarpa Makino (Lauraceae). These compounds inhibited chitin synthase 2 with IC(50) values of 23.3, 21.4 and 23.8 microg/mL, respectively. Methyllinderone (1) and linderone (2) exhibited no inhibitory activities for chitin synthases 1 and 3 from S. cerevisiae, and chitin synthase 1 from Candida albicans up to the concentration of 280 microg/mL, while kanakugiol (3) exhibited very weak activity against chitin synthase 1 of C. albicans with an IC(50) of 160 microg/mL. All of the compounds showed moderate to weak antifungal activities against various pathogenic fungi (MIC: 8 - >128 microg/mL) including Cryptococcus neoformans, Aspergillus fumigatus, and Colletotrichum lagenarium. The results indicate that these compounds are specific inhibitors of chitin synthase 2 and can potentially serve as antifungal agents.
Hwang
Eui Il
EI
KT&G Central Research Institute, Daejeon, Korea.
Lee
Yun Mi
YM
Lee
Sang Myung
SM
Yeo
Woon Hyung
WH
Moon
Jae Sun
JS
Kang
Tae Hoon
TH
Park
Ki Duk
KD
Kim
Sung Uk
SU
D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002176:Candida albicans / Q000187:drug effects / Q000201:enzymology; D002687:Chitin Synthase / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D020128:Inhibitory Concentration 50; D017705:Lignans / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D027443:Lindera; D008826:Microbial Sensitivity Tests; D003904:Mitosporic Fungi / Q000187:drug effects; D008517:Phytotherapy; D024301:Plant Bark; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D017705:Lignans; D010936:Plant Extracts; D002687:Chitin Synthase; C400821:chitin synthase 2