- Title
- Synthetic analogues of the marine bisindole deoxytopsentin: potent selective inhibitors of MRSA pyruvate kinase
- Creator
- Veale, Clinton G L, Zoraghi, Roya, Young, Ryan M, Morrison, James P, Pretheeban, Manoj, Lobb, Kevin A, Reiner, Neil E, Andersen, Raymond J, Davies-Coleman, Michael T
- Subject
- To be catalogued
- Date
- 2015
- Type
- text
- Type
- article
- Identifier
- http://hdl.handle.net/10962/448045
- Identifier
- vital:74693
- Identifier
- xlink:href="https://doi.org/10.1021/np500755v"
- Description
- As part of an ongoing study to elucidate the SAR of bisindole alkaloid inhibitors against the evolutionary conserved MRSA pyruvate kinase (PK), we present here the synthesis and biological activity of six dihalogenated analogues of the naturally occurring sponge metabolite deoxytopsentin, including the naturally occurring dibromodeoxytopsentin. The most active compounds displayed potent low nanomolar inhibitory activity against MRSA PK with concomitant significant selectivity for MRSA PK over human PK orthologues. Computational studies suggest that these potent MRSA PK inhibitors occupy a region of the small interface of the enzyme tetramer where amino acid sequence divergence from common human PK orthologues may contribute to the observed selectivity.
- Format
- computer, online resource, application/pdf, 1 online resource (8 pages), pdf
- Publisher
- ACS Publications
- Language
- English
- Relation
- Journal of Natural Products, Veale, C.G., Zoraghi, R., Young, R.M., Morrison, J.P., Pretheeban, M., Lobb, K.A., Reiner, N.E., Andersen, R.J. and Davies-Coleman, M.T., 2015. Synthetic analogues of the marine bisindole deoxytopsentin: potent selective inhibitors of MRSA pyruvate kinase. Journal of natural products, 78(3), pp.355-362, Journal of Natural Products volume 78 number 3 p. 355 2015 1520-6025
- Rights
- Publisher
- Rights
- Use of this resource is governed by the terms and conditions of the ACS Publications Terms of Use Statement (https://0-www.acs.org.wam.seals.ac.za/content/acs/en/terms.html)
- Rights
- Closed Access
- Hits: 139
- Visitors: 139
- Downloads: 3
Collections
Veale, Clinton G L (Dr)
Lobb, Kevin Allan (Assoc Prof)
RU Department of Chemistry
SDG 03. Good Health and Well-Being
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | SOURCE1 | Synthetic analogues of the marine bisindole deoxytopsentin.pdf | 731 KB | Adobe Acrobat PDF | View Details Download |