title: Inhibition of the Calcineurin Pathway by Two Flavonoids Isolated fromMiliusa sinensisFinet & Gagnep.
abstract: In order to discover plant-derived signaling pathway inhibitors with antifungal properties, a two-component screening system utilizing the calcineurin and Hog1 mitogen-activated protein kinase pathways responsible for the virulence networks ofCryptococcus neoformanswas employed, owing to the counter-regulatory actions of these pathways. Of the 1,000 plant extracts tested, two bioactive compounds fromMiliusa sinensiswere found to act specifically on the calcineurin pathway ofC. neoformans. These compounds, identified as pashanone and 5-hydroxy-6,7-dimethoxyflavanone, exhibited potent antifungal activities against various human pathogenic fungi with minimum inhibitory concentration values ranging from 4.0 to >128 μg/ml.
authors.affiliation: Division of Systems Biology and Bioengineering, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea.
authors.forename: Won Jeong
authors.initials: WJ
authors.lastname: Lee
authors.affiliation: Division of Systems Biology and Bioengineering, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea.
authors.forename: Jae Sun
authors.initials: JS
authors.lastname: Moon
authors.affiliation: Division of Systems Biology and Bioengineering, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea.
authors.forename: Young Tae
authors.initials: YT
authors.lastname: Kim
authors.affiliation: Vietnam Academy of Science and Technology (VAST), Hanoi 10307, Vietnam.
authors.forename: Tran The
authors.initials: TT
authors.lastname: Bach
authors.affiliation: Vietnam Academy of Science and Technology (VAST), Hanoi 10307, Vietnam.
authors.forename: Do Van
authors.initials: DV
authors.lastname: Hai
authors.affiliation: Division of Systems Biology and Bioengineering, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea.
authors.forename: Sung Uk
authors.initials: SU
authors.lastname: Kim
mesh_terms: D029061:Annonaceae / Q000737:chemistry*; D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D019703:Calcineurin / Q000378:metabolism*; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D053858:Metabolic Networks and Pathways / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D010936:Plant Extracts / Q000737:chemistry
chemical_list: D000935:Antifungal Agents; D005419:Flavonoids; D010936:Plant Extracts; D019703:Calcineurin
keywords: Cryptococcus neoformans; Miliusa sinensis Finet & Gagnep.; calcineurin pathway; two-component system; virulence network