Comparative chemoreactome analysis of dexketoprofen, ketoprofen, and diclofenac
Abstract
Cyclooxygenase-2 (COX-2) is the main targeted protein of non-steroidal anti-inflammatory drugs (NSAID); nevertheless, the latter substantially differ in pharmacological properties.
Objective: to establish the spectrum of pharmacological actions of dexketoprofen, ketoprofen, and diclofenac, by using a chemoreactome analysis.
Material and methods. A chemoinformation analysis was used to determine a list of the chemical structures closest to dexketoprofen. For each molecule, the investigators extracted the results of experimental measurements of the rheological properties of this molecule from databases and a chemoreactome analysis was carried out. The comparative chemoreactome analysis of the molecule of dexketoprofen and control molecules (ketoprofen, diclofenac) could assess the biological activity of the studied molecule.
Results and discussion. Unlike the molecules of comparison, dexketoprofen was found to be able to accumulate mainly in muscles, adipose tissue, and adrenal glands. The anti-inflammatory and analgesic effect of dexketoprofen can be carried out via modulation not only of the metabolism of prostaglandins, but also that of leukotrienes and encephalins, as well as via inhibition of metalloproteinases and glutamate receptors. In addition, the analysis showed a considerable difference in the interaction profiles of dexketoprofen, ketoprofen, and diclofenac with cytochrome P450 enzymes. Dexketoprofen can enhance the efficacy of anti-arrhythmic and antiadrenergic agents, whereas ketoprofen and diclofenac are able to negatively affect the metabolism of omega-3 polyunsaturated fatty acids and vitamin D.
Conclusion. The chemoreactome analysis could identify the promising vasodilatory, antiplatelet, antidiabetic, and antitumor effects of dexketoprofen in addition to its main action.
About the Authors
I. Yu. Torshin
Federal Research Center «Informatics and Control», Russian Academy of Sciences
Russian Federation
Russian Federation
Laboratory of Pharmacoinformatics,
40, Vavilov St., Moscow 119333
O. A. Gromova
Federal Research Center «Informatics and Control», Russian Academy of Sciences
Russian Federation
Russian Federation
Laboratory of Pharmacoinformatics,
40, Vavilov St., Moscow 119333
L E. Fedotova
Ivanovo State Medical Academy, Ministry of Health of Russia
Russian Federation
8, Sheremetevsky Pr., Ivanovo 153000
Russian Federation
8, Sheremetevsky Pr., Ivanovo 153000
A. N. Gromov
Federal Research Center «Informatics and Control», Russian Academy of Sciences
Russian Federation
Russian Federation
Laboratory of Pharmacoinformatics,
40, Vavilov St., Moscow 119333
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Review
For citations:
Torshin I.Yu., Gromova O.A., Fedotova L.E., Gromov A.N. Comparative chemoreactome analysis of dexketoprofen, ketoprofen, and diclofenac. Neurology, Neuropsychiatry, Psychosomatics. 2018;10(1):47-54. (In Russ.) https://doi.org/10.14412/2074-2711-2018-1-47-54
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