Chemoproteomic analysis of the promising candidate molecule of the indole derivative with lab code SV-1010 and other non-steroidal anti-inflammatory drugs

Authors

DOI:

https://doi.org/10.18413/rrpharmacology.10.497

Abstract

Introduction: For effective and safe pharmacotherapy of pain, it is important to evaluate the mechanisms and spectrum of action of non-steroidal anti-inflammatory drugs (NSAIDs), including their effect on the proteom, central effect, as well as pain relieving and anti-inflammatory effects. The aim of the study was to evaluate the complex of differences between the promising candidate-molecule of indole derivative SV-1010 and the well-known NSAIDs.

Materials and Methods: Chemoproteomic moduling of pharmacological effects of SV-1010 and NSAID diclofenac, nimesulide and ketorolac on the rat proteom by means of topological analysis of chemographs.

Results: The significant differences in the effects of the studied molecules were found for 820 proteins of the rat proteom. SV-1010, to a lesser degree than the other molecules, can inhibit dopamine D1- and D2-type receptors and, at the same time, stimulate the release of dopamine in the neostriatum (EC50 = 27 nM). SV-1010, to a greater extent than the other molecules, can inhibit the GABA conveyor (EC50 = 65 nM) and the NMDA receptors Grin1/Grin2b (IC50 175 nM). SV-1010 can activate Cannabinoid CB2 receptors, inhibit enzymes of leukotriene biosynthesis, CC receptors of pro-inflammatory chemokines and leukotrienes.

Conclusion: The chemoreactomic and chemoproteomic profiling of SV-1010 indicated its potential central effect through dopaminergic and GABA-neurotransmission and additional anti-inflammatory mechanisms, which can help increase pain-relieving effects.

Graphical Abstract

Keywords:

diclofenac, ketorolac, machine learning, nimesulide, chemoinformatics, indole derivative SV-1010

References

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Author Contribution

Pavel A. Galenko-Yaroshevsky, Kuban State Medical University

Сorresponding member of the Russian Academy of Sciences, Holder of Advanced Doctorate (Doctor of Science) in Medical Sciences, Professor, Head of the Department of Pharmacology, Kuban State Medical University, Krasnodar, Russia; е-mail: Galenko.Yaroсhevsky@gmail.com; ORCID ID https://orсid.org/0000-0003-3190-1437. The author’s contribution: concept development – shaping the idea and research direction; developing and designing methodology, and formulating the key aims and tasks.

Ivan Yu. Torshin, Federal Research Center “Informatics and Management” of the Russian Academy of Sciences

Candidate of Physical and Mathematical Sciences (PhD), Candidate of Chemical Sciences (PhD), lead research fellow, Federal Research Center “Informatics and Management” of the Russian Academy of Sciences, Moscow, Russia; е-mail: tiy135@yahoo.com; ORCID ID https://orcid.org/0000-0002-2659-7998. The author’s contribution: conducting research, developing and designing methodology, and writing the text of the article.

Andrey N. Gromov, Federal Research Center “Informatics and Management” of the Russian Academy of Sciences

Research engineer, Federal Research Center “Informatics and Management” of the Russian Academy of Sciences, Moscow, Russia; e-mail: gromlogin@gmail.com; ORCID ID https://orcid.org/0000-0001-7507-191X. The author’s contribution: conducting research, developing and designing methodology, and writing the text of the article.

Ivan A. Reyer, Federal Research Center “Informatics and Management” of the Russian Academy of Sciences

Candidate of Technical Sciences (PhD), research fellow, Federal Research Center “Informatics and Management” of the Russian Academy of Sciences, Moscow, Russia; e-mail: reyer@forecsys.ru; ORCID ID https://orcid.org/0000-0002-7928-053X. The author’s contribution: conducting research, developing and designing methodology, and writing the text of the article.

Olga A. Gromova, Federal Research Center “Informatics and Management” of the Russian Academy of Sciences

Holder of an Advanced Doctorate (Doctor of Science) in Medical Sciences, Professor, lead  research fellow, Federal Research Center “Informatics and Management” of the Russian Academy of Sciences, Moscow, Russia; e-mail: unesco.gromova@gmail.com; ORCID ID https://orcid.org/0000-0002-7663-710X. The author’s contribution: conducting research, developing and designing methodology, and writing the text of the article.

Tereza R. Glechyan, Kuban State Medical University

Teaching fellow, Department of Pharmacology, Kuban State Medical University, Krasnodar, Russia; e-mail: t_g91@mail.ruORCID ID  https://orсid.org/0009-0002-4983-2433. The author’s contribution: analyzing and interpreting the data obtained and participating in research design.

Konstantin F. Suzdalev, Southern Federal University

Candidate of Chemical Sciences (PhD), Associate Professor of the Department of Chemistry of Natural and High Molecular Compounds, Southern Federal University, Rostov-on-Don, Russia; е-mail: konsuz@gmail.com; ORCID ID https://orcid.org/0000-0003-4879-0577. The author’s contribution: analyzing and interpreting the research results and participating in research design.

Andrey V. Zadorozhniy, Rostov State Medical University

Candidate of Medical Sciences (PhD), Associate Professor, Head of the Department of Dentistry No. 4, Rostov State Medical University, Rostov-on-Don, Russia; e-mail: stomvr1@gmail.com; ORCID ID https://orcid.org/0000-0001-9552-8542. The author’s contribution: editing and preparing the article text, participating in research design, and correcting the final draft of the article.

Anait V. Zelenskaya, Kuban State Medical University

Candidate of Medical Sciences (PhD), Associate Professor, Department of Pharmacology, Kuban State Medical University, Krasnodar, Russia; е-mail: anait_06@mail.ru; ORCID ID https://orcid.org/0000-0001-9512-2526. The author’s contribution: analyzing and interpreting the research results, preparing and editing the text of the article, and participating in research design.

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Published

19-07-2024

How to Cite

Galenko-Yaroshevsky PA, Torshin IY, Gromov AN, Reyer IA, Gromova OA, Glechyan TR, Suzdalev KF, Zadorozhniy AV, Zelenskaya AV (2024) Chemoproteomic analysis of the promising candidate molecule of the indole derivative with lab code SV-1010 and other non-steroidal anti-inflammatory drugs. Research Results in Pharmacology 10(3): 1–9. https://doi.org/10.18413/rrpharmacology.10.497

Issue

Section

Experimental Pharmacology

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