Synthesis and biological evaluations of NO-donating oxa- and aza-pentacycloundecane derivatives as potential neuroprotective candidates

Simple item page
dc.contributor.authorSharma, Rajan
dc.contributor.authorJoubert, Jacques
dc.contributor.authorMalan, Sarel F.
dc.date.accessioned2018-02-06T12:06:39Z
dc.date.available2018-02-06T12:06:39Z
dc.date.issued2018
dc.description.abstractIn order to utilize the neuroprotective properties of polycyclic cage compounds, and explore the NO-donating ability of nitrophenyl groups, an array of compounds was synthesized where the different nitrophenyl groups were appended on oxa and aza-bridged cage derivatives. Biological evaluations of the compounds were done for cytotoxicity, neuroprotective abilities, the inhibition of N-methyl-D-aspartate (NMDA)-mediated Ca2+ influx, the inhibition of voltage-mediated Ca2+ influx, and S-nitrosylation abilities. All of the compounds showed low toxicity. With a few exceptions, most of the compounds displayed good neuroprotection and showed inhibitory activity for NMDA-mediated and voltage-gated calcium influx, ranging from high (>70%) to low (20–39%) inhibition. In the S-nitrosylation assay, the compounds with the nitro moiety as the NO-donating group exhibited low to good nitrosylation potency compared to the positive controls. From the biological evaluation of the tested compounds, it was not possible to obtain a simple correlation that could explain the results across all of the biological study domains. This can be ascribed to the independent processes evaluated in the different assays, which reiterate that neuroprotection is a result of multifactorial biochemical mechanisms and interactions. However, these results signify the important aspects of the pentacylcoundecylamine neuroprotectants across different biological study realms.en_US
dc.description.accreditationISI
dc.identifier.citationSharma, R. et al. (2018). Synthesis and biological evaluations of NO-donating oxa- and aza-pentacycloundecane derivatives as potential neuroprotective candidates. Molecules, 23: 308en_US
dc.identifier.issn1420-3049
dc.identifier.urihttp://dx.doi.org/10.3390/molecules23020308
dc.identifier.urihttp://hdl.handle.net/10566/3478
dc.language.isoenen_US
dc.privacy.showsubmitterFALSE
dc.publisherMDPIen_US
dc.rights© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
dc.status.ispeerreviewedTRUE
dc.subjectNO-donatingen_US
dc.subjectS-nitrosylationen_US
dc.subjectNeuroprotectionen_US
dc.subjectPolycyclic cageen_US
dc.subjectCalcium influxen_US
dc.titleSynthesis and biological evaluations of NO-donating oxa- and aza-pentacycloundecane derivatives as potential neuroprotective candidatesen_US
dc.typeArticleen_US

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Sharma_Synthesis-and-biological_2018.pdf
Size:
785.17 KB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

Research Articles (School of Pharmacy)