AUTHOR=Shah Abdul Bari , Baiseitova Aizhamal , Kim Jeong Ho , Lee Yong Hyun , Park Ki Hun 

TITLE=Inhibition of Bacterial Neuraminidase and Biofilm Formation by Ugonins Isolated From Helminthostachys Zeylanica (L.) Hook

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.890649

DOI=10.3389/fphar.2022.890649

ISSN=1663-9812

ABSTRACT=<p>Bacterial neuraminidase (BNA) plays a pivotal role in the pathogenesis of several microbial diseases including biofilm formation. The aim of this study is to reveal the neuraminidase inhibitory potential of metabolites from <italic>Helminthostachys zeylanica</italic> (L.) Hook. which have diverse biological activities including PTP1B and <italic>α</italic>-glucosidase. The six ugonins (<bold>1–6</bold>) from the target plant showed significant neuraminidase inhibition. The inhibitory potencies were observed at a nanomolar level of 35–50 nM, which means they are 100 times more active than their corresponding mother compounds (eriodyctiol and luteolin). A detailed kinetic study revealed that all ugonins were reversible noncompetitive inhibitors. An in-depth investigation of the most potent compound <bold>1</bold> showed its time-dependent inhibition with the isomerization model having <italic>k</italic><sub>5</sub> = 0.0103 min<sup>−1</sup>, <italic>k</italic><sub>6</sub> = 0.0486 min<sup>−1</sup>, and <italic>K</italic><sub>i</sub><sup>app</sup> = 0.062 μM. The binding affinities (<italic>K</italic><sub>sv</sub>) were agreed closely with our prediction based on the inhibitory potencies. Particularly, ugonin J (<bold>1</bold>) blocked the biofilm formation of <italic>E. coli</italic> dose-dependently up to 150 µM without the inhibition of bacteria. The major compounds (<bold>1–6</bold>) in the extract were characterized by UPLC-ESI-Q-TOF/MS.</p>