Highly potent bacterial neuraminidase inhibitors, chromenone derivatives from Flemingia philippinensis
- Wang, Yan; Kim, Jeong Yoon; Song, Yeong Hun; Li, Zuo Peng; Yoon, Sang Hwa; Uddin, Zia; Ban, Yeong Jun; Lee, Keun Woo; Park, Ki Hun
- Issue Date
- ELSEVIER SCIENCE BV
- Flemingia philippinensis; Bacterial neuraminidase; Novel chromenones
- INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, v.128, pp.149 - 157
- Journal Title
- INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
- Start Page
- End Page
- The chromenone derivatives (1-4) from the root part of Flemingia philippinensis showed a significant inhibition against bacterial neuraminidase (NA) which plays a pivotal role in a cellular interaction including pathogenesis of bacterial infection and subsequent inflammation. The compounds 1 and 2 were the new compounds, philippin D (1) and philippin E (2). In particular, compounds (1-3) exhibited sub micromolar levels of IC50 values with 0.75, 0.54, and 0.07 mu M. This is the first report that chromenone skeleton emerged as a lead structure of bacterial NA inhibition. In kinetic study, 8,8-diprenyl compounds displayed competitive inhibitory mode, whereas 4a,8-diprenyl ones showed noncompetitive behavior. It was manifested that all competitive inhibitors (1 and 2) were simple reversible slow-binding against bacterial NA. The binding affinities (K-SV) of inhibitors to enzyme were agreement with their respective inhibitory potencies. Molecular docking data confirmed that the position of 3-methyl-2-butenyl substituent affects inhibitory mechanism against CpNanI. The tri-arginyl cluster of R266, R555, and R615 and D291 in NanI tightly interact with the competitive inhibitors. (C) 2019 Published by Elsevier B.V.
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