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 IC(50)s between 0.12 and 22.03 mu M. In particular, amorisin 2 exhibited 120 nM IC50, 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 mu M) 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 mu M. (C) 2011 Elsevier Ltd. All rights reserved.