TY - JOUR
T1 - Novel curcumin analog (cis-trans curcumin) as ligand to adenosine receptors A2A and A2B
T2 - potential for therapeutics
AU - Hamilton, Luke J.
AU - Walker, Michaela
AU - Pattabiraman, Mahesh
AU - Zhong, Haizhen A.
AU - Luedtke, Brandon
AU - Chandra, Surabhi
N1 - Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2021/3
Y1 - 2021/3
N2 - All four of the adenosine receptor (AR) subtypes mediate pain and have been targeted by pharmacologists to generate new therapeutics for chronic pain. The vanilloid phytochemicals, which include curcumin, capsaicin, and gingerol, have been shown to alleviate pain. However, there is little to no literature on the interaction of vanilloid phytochemicals with ARs. In this study, photochemical methods were used to generate a novel isomer of curcumin (cis-trans curcumin or CTCUR), and the interactions of both curcumin and CTCUR with the two Gs-linked AR subtypes were studied. Competitive binding assays, docking analysis, and confocal fluorescence microscopy were performed to measure binding affinity; cell survival assays were used to measure toxicity; and cAMP assays were performed to measure receptor activation. Competitive binding results indicated that CTCUR binds to both AR A2A and AR A2B with Ki values of 5 μM and 7 μM, respectively, which is consistent with our docking results. Fluorescence microscopy data also shows binding for A2B and A2A. Cell survival results show that CTCUR and CUR are nontoxic at the tested concentrations in these cell lines. Overall, our results suggest that vanilloid phytochemicals may be slightly modified to increase interaction with Gs-ARs, and thereby can be further explored to provide a novel class of non-opioid antinociceptives.
AB - All four of the adenosine receptor (AR) subtypes mediate pain and have been targeted by pharmacologists to generate new therapeutics for chronic pain. The vanilloid phytochemicals, which include curcumin, capsaicin, and gingerol, have been shown to alleviate pain. However, there is little to no literature on the interaction of vanilloid phytochemicals with ARs. In this study, photochemical methods were used to generate a novel isomer of curcumin (cis-trans curcumin or CTCUR), and the interactions of both curcumin and CTCUR with the two Gs-linked AR subtypes were studied. Competitive binding assays, docking analysis, and confocal fluorescence microscopy were performed to measure binding affinity; cell survival assays were used to measure toxicity; and cAMP assays were performed to measure receptor activation. Competitive binding results indicated that CTCUR binds to both AR A2A and AR A2B with Ki values of 5 μM and 7 μM, respectively, which is consistent with our docking results. Fluorescence microscopy data also shows binding for A2B and A2A. Cell survival results show that CTCUR and CUR are nontoxic at the tested concentrations in these cell lines. Overall, our results suggest that vanilloid phytochemicals may be slightly modified to increase interaction with Gs-ARs, and thereby can be further explored to provide a novel class of non-opioid antinociceptives.
KW - 5'-N-Ethylcarboxamidoadenosine (PubChem CID: 4400)
KW - Adenosine
KW - Adenosine receptor A
KW - Adenosine receptor A
KW - Chronic pain
KW - Cis-Trans curcumin (PubChem CID: 969516)
KW - Curcumin
KW - Curcumin (PubChem CID: 969516)
KW - G
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U2 - 10.1016/j.phrs.2020.105410
DO - 10.1016/j.phrs.2020.105410
M3 - Article
C2 - 33401004
AN - SCOPUS:85099275520
SN - 1043-6618
VL - 165
JO - Pharmacological Research
JF - Pharmacological Research
M1 - 105410
ER -