Date of Award


Document Type


Degree Name

Master of Science (MS)



First Advisor

Surabhi Chandra

Committee Members

Kimberly Carlson, Allen Thomas, Nicholas Hobbs


adenosine receptors;binding affinity;cAMP;curcumin;pain;vanilloid phytochemicals


Vanilloid phytochemicals (VPs), which contain the 4-hydroxy-3-methoxybenzyl group, have consistently been shown to alleviate pain. All four of the adenosine receptor (AR) subtypes mediate pain and have been targeted by pharmacologists to generate new therapeutics for pain. However, despite the fact that both VPs and ARs are connected to pain relief, only a few studies have described the interaction between VPs and ARs. Furthermore, the few studies that have been done have all been performed in vivo, with no assessment of binding affinity and receptor activation in vitro. In this study, photochemical methods were used to generate a novel isomer of curcumin called cis-trans curcumin (CTCUR), and the interactions of CTCUR with each of the four AR subtypes were measured. Cell survival assays were performed to measure toxicity. Competitive binding assays, confocal fluorescence microscopy, and docking analysis were performed to measure binding affinity. Finally, cAMP immunoassays were performed to measure receptor activation. Binding assay results indicated that CTCUR has Ki values of 306 nM, 400 nM, 5,107 nM, and 6,722 nM at AR subtypes A1, A3, A2A, and A2B, respectively. These values suggest that CTCUR is selective for Gi-linked ARs over Gs-linked ARs. Docking studies likewise indicated that CTCUR interacts more strongly with the Gi-linked subtypes. Data from cAMP immunoassays at all four subtypes suggest that CTCUR is an agonist of ARs. Docking indicated that CTCUR binds to the toggle switch domain of ARs, which likewise suggests agonistic activity. Thus, this study provides the first in vitro and in silico data that support the hypothesis that ARs may serve as a mechanism of action for the antinociceptive effect of VPs.

Included in

Pharmacology Commons



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