title: Human neutrophil elastase inhibitory potential of flavonoids from Campylotropis hirtella and their kinetics.
abstract: Campylotropis hirtella is used as a food supplement in the subtropical region of China. In an intensive hunt for human neutrophil elastase inhibitors, we isolated eight flavonoids from C. hirtella three of which (1-3) emerged to be elastase inhibitors. Geranylated flavonoids (1-3) displayed significant inhibitory activity with IC50s between 8.5 and 30.8 μM. The most striking example was geranylated isofavanone 3 that inhibited elastase significantly (IC50=30.8 μM) but its parent compound (dalbergioidin) and isoflavone analog (5) were inactive (IC50>200 μM). Compounds (1-3) displayed different kinetic mechanisms (noncompetitive, competitive, and mixed type, respectively) that were dependent upon the parent skeleton. The competitive inhibitor, isoflavan-3-ol-4-one 2 manifested an inhibition of isomerization profile for elastase with kinetic parameters K5=0.0386 M-1S-1, K6=0.0244 μM-1S-1and Kiapp= 16.3427 μM. The specific identification of metabolites was accomplished by LC-DAD-ESI/MS that was also used to analyze abundance of active components (1-3) within the plant.
authors: a Division of Applied Life Science (BK21 Plus) , IALS, Gyeongsang National University , Jinju , Republic of Korea and.
authors: Xue Fei
authors: XF
authors: Tan
authors: a Division of Applied Life Science (BK21 Plus) , IALS, Gyeongsang National University , Jinju , Republic of Korea and.
authors: Dae Wook
authors: DW
authors: Kim
authors: a Division of Applied Life Science (BK21 Plus) , IALS, Gyeongsang National University , Jinju , Republic of Korea and.
authors: Yeong Hun
authors: YH
authors: Song
authors: a Division of Applied Life Science (BK21 Plus) , IALS, Gyeongsang National University , Jinju , Republic of Korea and.
authors: Jeong Yoon
authors: JY
authors: Kim
authors: a Division of Applied Life Science (BK21 Plus) , IALS, Gyeongsang National University , Jinju , Republic of Korea and.
authors: Heung Joo
authors: HJ
authors: Yuk
authors: a Division of Applied Life Science (BK21 Plus) , IALS, Gyeongsang National University , Jinju , Republic of Korea and.
authors: Yan
authors: Y
authors: Wang
authors: b Department of Chemistry and Chemical Biology , Cornell University , Ithaca , NY , USA.
authors: Marcus J
authors: MJ
authors: Curtis-Long
authors: a Division of Applied Life Science (BK21 Plus) , IALS, Gyeongsang National University , Jinju , Republic of Korea and.
authors: Ki Hun
authors: KH
authors: Park
mesh_terms: D004305:Dose-Response Relationship, Drug; D007887:Fabaceae / Q000737:chemistry*; D005419:Flavonoids / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015394:Molecular Structure; D053491:Proteinase Inhibitory Proteins, Secretory / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D005419:Flavonoids; D053491:Proteinase Inhibitory Proteins, Secretory; D019272:Leukocyte Elastase
keywords: Camplyotropis hirtella; LC-DAD-ESI/MS; competitive inhibition; geranylated isoflavanone; human neutrophil elastase