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Comparative chemoreactome analysis of dexketoprofen, ketoprofen, and diclofenac

https://doi.org/10.14412/2074-2711-2018-1-47-54

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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

Laboratory of Pharmacoinformatics, 

40, Vavilov St., Moscow 119333



O. A. Gromova
Federal Research Center «Informatics and Control», Russian Academy of Sciences
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


A. N. Gromov
Federal Research Center «Informatics and Control», Russian Academy of Sciences
Russian Federation

Laboratory of Pharmacoinformatics, 

40, Vavilov St., Moscow 119333



References

1. Халикова ЕЮ. Декскетопрофена трометамол в амбулаторном обезболивании. Consilium Medicum. Хирургия. 2011;(1):5-10. [Khalikova EYu. Dexketoprofen trometamol in outpatient anesthesia. Consilium Medicum. Khirurgiya. 2011;(1):5-10. (In Russ.)].

2. Moore RA, Barden J. Systematic review of dexketoprofen in acute and chronic pain. BMC Clin Pharmacol. 2008 Oct 31;8:11. doi: 10.1186/1472-6904-8-11.

3. Wakimoto N, Wolf I, Yin D, et al. Nonsteroidal Anti-inflammatory Drugs Suppress Glioma via 15-Hydroxyprostaglandin Dehydrogenase. Cancer Res. 2008 Sep 1;68(17): 6978-86. doi: 10.1158/0008-5472.CAN-07-5675.

4. Graham DJ. COX-2 inhibitors, other NSAIDs, and cardiovascular risk: the seduction of common sense. JAMA. 2006 Oct 4;296(13): 1653-6. Epub 2006 Sep 12.

5. Torshin IYu. Bioinformatics in the postgenomic era: physiology and medicine. New York: NovaBiomedicalBooks; 2007.

6. Журавлёв ЮИ, Рудаков КВ, Торшин ИЮ. Алгебраические критерии локальной разрешимости и регулярности как инструмент исследования морфологии аминокислотных последовательностей. Труды МФТИ. 2011;3(4):67-76. [Zhuravlev YuI, Rudakov KV, Torshin IYu. Algebraic criteria of local solvability and regularity as a tool for studying the morphology of amino acid sequences. Trudy MFTI. 2011;3(4):67-76. (In Russ.)].

7. Рудаков КВ, Торшин ИЮ. Об отборе информативных значений признаков на базе критериев разрешимости в задаче распознавания вторичной структуры белка. ДАН. 2011;(1):1-5. [Rudakov KV, Torshin IYu. About selection of informative values of signs on the basis of solvability criteria in the problem of recognition of secondary structure of protein. DAN. 2011;(1):1-5. (In Russ.)].

8. Журавлев ЮИ. Об алгебраическом подходе к решению задач распознавания или классификации. Проблемы кибернетики. 1978; (3):5-68. [Zhuravlev YuI. On an algebraic approach to solving recognition or classification problems. Problemy kibernetiki. 1978;(3):5-68. (In Russ.)].

9. Торшин ИЮ, Громова ОА. Экспертный анализ данных в молекулярной фармакологии. Москва: МЦНМО; 2012. 768 с. [Torshin IYu, Gromova OA. Ekspertnyi analiz dannykh v molekulyarnoi farmakologii [Expert data analysis in molecular pharmacology]. Moscow: MTsNMO; 2012. 768 p.]

10. Cheng T, Pan Y, Hao M, Wang Y, Bryant SH. PubChem applications in drug discovery: a bibliometric analysis. Drug Discov Today. 2014 Nov;19(11):1751-1756.

11. Wishart DS, Tzur D, Knox C, et al. HMDB: the Human Metabolome Database. Nucleic Acids Res. 2007 Jan;35(Database issue):D521-6.

12. Si H, Liu D. Phytochemical genistein in the regulation of vascular function: new insights. Curr Med Chem. 2007;14(24):2581-9.

13. Onaka Y, Shintani N, Nakazawa T, et al. Prostaglandin D2 signaling mediated by the CRTH2 receptor is involved in MK-801-induced cognitive dysfunction. Behav Brain Res. 2016 Nov 1;314:77-86. doi: 10.1016/j.bbr.2016. 07.050. Epub 2016 Jul 29.

14. Joo HW, Kang YR, Kwack MH, Sung YK. 15-deoxy prostaglandin J2, the nonenzymatic metabolite of prostaglandin D2, induces apoptosis in keratinocytes of human hair follicles: a possible explanation for prostaglandin D2-mediated inhibition of hair growth. Naunyn Schmiedebergs Arch Pharmacol. 2016 Jul;389(7): 809-13. doi: 10.1007/s00210-016-1257-z. Epub 2016 May 17.

15. Meyer HC. Alopecia associated with ibuprofen. JAMA. 1979 Jul 13;242(2):142.

16. Tang Y, Fung E, Xu A, Lan HY. C-reactive protein and ageing. Clin Exp Pharmacol Physiol. 2017 Dec;44 Suppl 1:9-14. doi: 10.1111/1440-1681.12758. Epub 2017 Aug 24.

17. Benson C, Mifflin K, Kerr B, et al. Biogenic Amines and the Amino Acids GABA and Glutamate: Relationships with Pain and Depression. Mod Trends Pharmacopsychiatry. 2015;30:67-79. doi: 10.1159/000435933. Epub 2015 Sep 18.


For citation:


Torshin I.Y., 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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ISSN 2074-2711 (Print)
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