Rapid identification of isoprenylated flavonoids constituents with inhibitory activity on bacterial neuraminidase from root barks of paper mulberry (Broussonetia papyrifera)

• Main Authors: Jang, H.-J (Author), Jung, S. (Author), Kim, D.-Y (Author), Kim, W.J (Author), Lee, J. (Author), Lee, S.U (Author), Lim, G. (Author), Oh, S.-R (Author), Park, M.H (Author), Ryu, H.W (Author), Yuk, H.J (Author)
• Format: Article
• Language: English
• Published: Elsevier B.V. 2021
• Subjects: 3' (3 methylbut 2 enyl) 3',4',7 trihydroxyflavane; 3,4 dihydroxyisolonchocarpin; 4 hydroxyisolonchocarpin; 8 (1,1 dimethylallyl) 5' (3 methylbut 2 enyl) 3',4',5,7 tetrahydroxyflanvonol; Affinity-based ultrafiltration; antiinfective agent; Article; Bacterial neuraminidase docking; bacteriostatic activity; bark; binding affinity; broussochalcone A; broussochalcone B; broussoflavan A; broussoflavonol B; Broussonetia; Broussonetia papyrifera; Broussonetia papyrifera roots; chalcone; Chalcone; chalcone derivative; Chalcones; chemistry; controlled study; drug effect; drug identification; drug isolation; drug mechanism; drug potency; enzyme inhibition; flavan derivative; flavonoid; Flavonoids; flavonol derivative; Flavonols; IC50; isolation and purification; isoprenylation; kazinol A; kazinol B; kazinol B1; kazinol E; kinetics; Kinetics; metabolism; Neuraminidase; nonhuman; papyriflavonol A; physiology; Plant Bark; plant extract; Plant Extracts; plant root; Plant Roots; polyphenol; Polyphenols; prenylation; Prenylation; quercetin; sialidase; time of flight mass spectrometry; ultra performance liquid chromatography; ultrafiltration; unclassified drug
• Online Access: View Fulltext in Publisher

 This study was to assess the possibility of using competitive and slow binding experiments with affinity-based ultrafiltration UPLC-QTof-MS analysis to identify potent bacterial neuraminidase (bNA) inhibitors from the Broussonetia papyrifera roots extract. To isolate unbound compounds from the enzyme-binding complex, the root bark extracts were either incubated in the absence of bNA, in the presence of bNA, or with the time-dependent bNA before the ultrafiltration was performed. Thirteen flavonoids were separated from the target extract, and their inhibitory activities were tested against bNA. The isolated flavonoids exhibited potent inhibition against NA (IC50 = 0.7–54.0 μM). Our kinetic analysis of representative active flavonoids (1, 2, and 6) showed slow and time-dependent reversible inhibition. Additionally, chalcones exhibited noncompetitive inhibition characteristics, whereas flavonols and flavans showed mixed-type behavior. The computational results supported the experimental behaviors of flavonoids 2, 6, 10, and 12, indicating that bounded to the active site, but flavonoids 6 and 10 binds near but not accurately at the active site. Although this is mixed-type inhibition, their binding can be considered competitive. © 2021