Abstract
Previously, a novel lignan sevanol was isolated from Thymus armeniacus, its structure was elucidated; and it was shown that it efficiently inhibits the operation of acid-sensing ion channel ASIC3 and exhibits a pronounced analgesic and anti-inflammatory effect. In this work, the biological activity of a synthetic analogue of sevanol, its stereoisomer, and a precursor compound that represents half of the sevanol molecule was measured in electrophysiological experiments on human ASIC3 channels expressed in Xenopus laevis oocytes. The measured inhibitory activity of a synthetic analogue coincided with the activity of the natural sample; the inhibitory activity of stereoisomer was approximately three times lower, and the precursor was an even less effective inhibitor. Thus, it was shown that the functional groups and stereo configuration of sevanol are essential for its biological activity, which is important to consider while planning the optimal method of its synthesis and development of pharmaceuticals based thereon.
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Abbreviations
- ASIC:
-
acid-sensing ion channel
- BSA:
-
bovine serum albumin
- HEPES:
-
4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid
- IC50 :
-
half maximal inhibitory concentration
- RP-HPLC:
-
reversed-phase high performance liquid chromatography
- TFA:
-
trifluoroacetic acid
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Adapted from a report presented at the VII Russian Symposium “Proteins and Peptides” (Novosibirsk, July 12–17, 2015).
Original Russian Text © D.I. Osmakov, S.G. Koshelev, O.A. Belozerova, V.S. Kublitski, Ya.A. Andreev, E.V. Grishin, S.A. Kozlov, 2015, published in Bioorganicheskaya Khimiya, 2015, Vol. 41, No. 5, pp. 606–611.
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Osmakov, D.I., Koshelev, S.G., Belozerova, O.A. et al. Biological activity of sevanol and its analogues. Russ J Bioorg Chem 41, 543–547 (2015). https://doi.org/10.1134/S1068162015050106
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DOI: https://doi.org/10.1134/S1068162015050106