Chemoproteomic analysis of tenoxicam compared with other nonsteroidal anti-inflammatory drugs

Background. Organization of effective and safe pharmacotherapy for pain and inflammation requires knowledge of the mechanisms and spectrum of action of nonsteroidal anti-inflammatory drugs (NSAIDs). These concern their anti-inflammatory, analgesic (including central) effects, effects on the proteome, micronutrient metabolism and other aspects of the body's metabolism depending on the administration route.

Objective: To compare the effects of tenoxicam, meloxicam, celecoxib, ketoprofen, nimesulide, diclofenac, ibuprofen molecules using the methods of chemoreactomic, chemoproteomic and pharmacoinformatic analysis.

Material and methods. The comparison of tenoxicam with other NSAIDs was conducted using the methods of topological analysis of Yu.I. Zhuravlev and K.V. Rudakov scientific school. These methods were developed based on the combinatorial theory of solvability and the classification theory of feature values ​​as applied to chemographs, i.e. mathematical structures describing the chemical structures of molecules.

Results. In silico estimates of anti-inflammatory, central, and analgesic effects of tenoxicam and comparison molecules were obtained. The profiles of belonging to various anatomical-therapeutic-chemical classification groups and the profiles of side effect frequencies of the NSAIDs (including the effect on micronutrient metabolism through the loss of vitamins and microelements) were analyzed. A comparison of the effects of molecules under oral, topical and parenteral administration was carried out. The profile of the pharmacological effects of tenoxicam differed significantly from those of other NSAIDs, indicating, in particular, potential antithrombotic, hypoglycemic, and antihistamine effects. Tenoxicam, unlike other molecules, exhibits a significant effect on the synthesis, secretion and activity of leukotriene B4 along with inhibitory effects on kinin receptors. In comparison with other NSAIDs, tenoxicam does not stimulate stronger losses of micronutrients. Chemoreactome assessments of the central effects of tenoxicam showed its comparability with other NSAIDs. The effects of tenoxicam under its topical, oral and parenteral administration are comparable to the anti-inflammatory action of other NSAIDs. The frequency analysis of various side effects, averaged over the studied sample of side effects, showed that tenoxicam was characterized by the lowest frequency of all the indicated side effects (3%; other molecules: 4–7%).

Conclusion. The chemoreactomic, chemoproteomic and pharmacoinformatic profiling of tenoxicam indicated its improved efficacy-safety balance compared to other NSAIDs.

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