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Brain Sciences Special Issue: Neuroprotection against Ischemic Brain Injury
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Brain Sci. 2015, 5(2), 130-143; doi:10.3390/brainsci5020130

Increasing the Biological Stability Profile of a New Chemical Entity, UPEI-104, and Potential Use as a Neuroprotectant Against Reperfusion-Injury

1
Department of Biomedical Sciences, Atlantic Veterinary College, Charlottetown, PE C1A 4P3, Canada
2
Department of Chemistry, University of Prince Edward Island, Charlottetown, PE C1A 4P3, Canada
*
Author to whom correspondence should be addressed.
Academic Editor: Bruno Meloni
Received: 11 March 2015 / Revised: 1 April 2015 / Accepted: 13 April 2015 / Published: 21 April 2015
(This article belongs to the Special Issue Neuroprotection against Ischemic Brain Injury)
View Full-Text   |   Download PDF [191 KB, uploaded 21 April 2015]   |  

Abstract

Previous work in our laboratory demonstrated the utility of synthetic combinations of two naturally occurring, biologically active compounds. In particular, we combined two known anti-oxidant compounds, lipoic acid and apocynin, covalently linked via an ester bond (named UPEI-100). In an animal model of ischemia-reperfusion injury (tMCAO), UPEI-100 was shown to produce equivalent neuroprotection compared to each parent compound, but at a 100-fold lower dose. However, it was determined that UPEI-100 was undetectable in any tissue samples almost immediately following intravenous injection. Therefore, the present investigation was done to determine if biological stability of UPEI-100 could be improved by replacing the ester bond with a more bio cleavage-resistant bond, an ether bond (named UPEI-104). We then compared the stability of UPEI-104 to the original parent compound UPEI-100 in human plasma as well as liver microsomes. Our results demonstrated that both UPEI-100 and UPEI-104 could be detected in human plasma for over 120 min; however, only UPEI-104 was detectable for an average of 7 min following incubation with human liver microsomes. This increased stability did not affect the biological activity of UPEI-104 as measured using our tMCAO model. Our results suggest that combining compounds using an ether bond can improve stability while maintaining biological activity. View Full-Text
Keywords: stroke; ischemia/reperfusion; middle cerebral artery occlusion; antioxidant therapy; neuroprotection; bio cleavage-resistance stroke; ischemia/reperfusion; middle cerebral artery occlusion; antioxidant therapy; neuroprotection; bio cleavage-resistance
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Saleh, T.M.; Connell, B.J.; Kucukkaya, I.; Abd-El-Aziz, A.S. Increasing the Biological Stability Profile of a New Chemical Entity, UPEI-104, and Potential Use as a Neuroprotectant Against Reperfusion-Injury. Brain Sci. 2015, 5, 130-143.

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