title: Flavanones and rotenoids from the roots of Amorpha fruticosa L. that inhibit bacterial neuraminidase.
abstract: Neuraminidase is a proven target in anti-viral drug development. It also appears to be important for infection by certain pathogenic bacteria and has been implicated in biofilm formation. Based on activity-guided fractionation, the acetone extract of Amorpha fruticosa roots gave four flavanones 1-4 and three rotenoids 5-7 which were identified as amoradicin (1), amorisin (2), isoamoritin (3), amoricin (4), amorphigeni (5), dalbinol (6), and 6-ketodehydroamorphigenin (7), respectively. All isolated inhibitors showed strong neuraminidase inhibition with IC₅₀s between 0.12 and 22.03 μM. In particular, amorisin 2 exhibited 120 nM IC(₅₀, which is 30-fold more potent than the positive control, quercetin. In addition, this is the first report detailing rotenoids (IC₅₀ = 8.34-16.74 μM) exhibiting neuraminidase inhibition. Kinetic analysis revealed that all inhibitors were noncompetitive. The most active neuraminidase inhibitors (2, 3, 5, 6) were proven to be present in the native root in high quantities by HPLC. Finally, at concentrations where no toxicity was observed, 3 and 6 inhibited Pseudomonas aeruginosa biofilm production. 29.7% and 21.0% inhibition respectively was observed at 25 μΜ.
authors.affiliation: Division of Applied Life Science (BK21 Program), IALS, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Young Soo
authors.initials: YS
authors.lastname: Kim
authors.forename: Young Bae
authors.initials: YB
authors.lastname: Ryu
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Curtis-Long
authors.forename: Heung Joo
authors.initials: HJ
authors.lastname: Yuk
authors.forename: Jung Keun
authors.initials: JK
authors.lastname: Cho
authors.forename: Jun Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Kwang Dong
authors.initials: KD
authors.lastname: Kim
authors.forename: Woo Song
authors.initials: WS
authors.lastname: Lee
authors.forename: Ki Hun
authors.initials: KH
authors.lastname: Park
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007887:Fabaceae / Q000737:chemistry*; D044950:Flavanones / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007700:Kinetics; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000201:enzymology; D012402:Rotenone / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D044950:Flavanones; D010936:Plant Extracts; D012402:Rotenone; D009439:Neuraminidase