title: Inhibition of chitin synthase 2 and antifungal activity of lignans from the stem bark of Lindera erythrocarpa.
abstract: 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.
authors.affiliation: KT&G Central Research Institute, Daejeon, Korea.
authors.forename: Eui Il
authors.initials: EI
authors.lastname: Hwang
authors.forename: Yun Mi
authors.initials: YM
authors.lastname: Lee
authors.forename: Sang Myung
authors.initials: SM
authors.lastname: Lee
authors.forename: Woon Hyung
authors.initials: WH
authors.lastname: Yeo
authors.forename: Jae Sun
authors.initials: JS
authors.lastname: Moon
authors.forename: Tae Hoon
authors.initials: TH
authors.lastname: Kang
authors.forename: Ki Duk
authors.initials: KD
authors.lastname: Park
authors.forename: Sung Uk
authors.initials: SU
authors.lastname: Kim
mesh_terms: 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
chemical_list: D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D017705:Lignans; D010936:Plant Extracts; D002687:Chitin Synthase; C400821:chitin synthase 2