Authors: Pavel A. Galenko-Yaroshevsky | Alina V. Sergeeva | I. Yu. Torshin | А. Н. Громов | О. А. Громова | Б. А. Трофимов | L. N. Parshina | Р. А. Мурашко | A. V. Zadorozhniy | A. V. Zelenskaya | Sergey Sergeev | Yu. V. Tovkach | O. N. Gulevskaya | I. V. Sholl
Source: FARMAKOEKONOMIKA Modern Pharmacoeconomics and Pharmacoepidemiology (article, 2024-12-20)
Field: Chemistry — Organic Chemistry

Chemoreactome prediction of anti-inflammatory, analgesic, ulcerogenic effects of the candidate molecule N-allylimidazole-zinc in comparison with zinc derivatives of nonsteroidal anti-inflammatory drugs Background. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used for effective and safe pharmacotherapy of inflammation and pain. NSAIDs usually reduce the level of gastroprotective prostaglandin E2 due to cyclooxygenase-1 inhibition. The zinc-containing candidate molecule N-allylimidazole-zinc (bis-(N-allylimidazole) zinc diacetate) is a promising anti-inflammatory drug, potentially devoid of gastrotoxicity. Objective : chemoreactome modeling of the pharmacological effects of N-allylimidazole-zinc and zinc derivatives of known NSAIDs (diclofenac, nimesulide, ketorolac) using topological analysis of chemographs of numerical prediction in complex feature systems. Material and methods. In silico modeling of the candidate molecule N-allylimidazole-zinc synthesized at Federal Research Center “Favorsky Irkutsk Institute of Chemistry” (Siberian Branch of Russian Academy of Sciences), was carried out using a conglomerate of chemoinformatic molecule analysis methods of Yu.I. Zhuravlev scientific school. These methods include the theory of chemograph analysis, methods for predicting numerical target variables, combinatorial theory of solvability/regularity, topological data analysis. Chemoreactome, pharmacoinformation and chemoneurocytological methods of analyzing the molecules properties are based on chemoreactome methodology, the latest direction in the application of machine learning systems in the field of postgenomic pharmacology. The pharmacological capabilities of molecules within chemoreactome methodology are assessed by comparing the chemical structure of racetam molecules with the structures of molecules for which the molecular pharmacological properties have been studied using artificial intelligence learning algorithms based on big data information presented in PubChem, HMDB, STRING, PharmGKB databases. Based on the entire complex of differences between molecules in interactions with receptor proteins, the “anti-obesity” score was calculated for each as the serial number of this molecule when sorting in descending order the values of the corresponding chemoreactome constants. Results . It was shown that N-allylimidazole-zinc may have anti-inflammatory effect due to the influence on cytokine activity and, in part, on prostaglandin and leuktriene metabolism. Its central effects are comparable to the effects of zinc-NSAIDs. The analgesic potential of N-allylimidazole-zinc may be associated with the inhibition of kinin receptors, weak antihistaminic and antinociceptive properties. The molecule may exhibit a protective effect on epithelial gastric mucosa and does not impair the properties of the stomach mucosal protective layer. It has been shown that N-allylimidazole-zinc, compared to other compounds included in the analysis, has the least negative effect on the metabolism of various vitamins and microelements. Conclusion . Chemoreactome profiling of N-allylimidazole-zinc indicates the prospects for its use as an anti-inflammatory drug. Zinc ; Analgesic ; Anti-inflammatory ; Pharmacology ; Medicine ; Chemistry ; Organic chemistry Synthesis and biological activity ; Computational Drug Discovery Methods ; Synthesis and Characterization of Heterocyclic Compounds