Chemoreactomic analysis of the drug prototype pilim-1 in comparison with zinc derivatives of nonsteroidal anti-inflammatory drugs

Background. Gastroenterological side effects (esophageal, gastric, and intestinal erosions) associated with the use of drugs from the group of nonsteroidal anti-inflammatory drugs (NSAIDs) highlight the need to explore new molecule candidates with reduced ulcerogenic effects. The zinc-containing molecule candidate pilim-1 has the potential to exhibit anti-inflammatory effects and improve the regenerative properties of the gastric mucosa. Objective: To explore the anti-inflammatory, ulcerogenic, analgesic, and antivitamin effects of the pilim-1 molecule using chemoreactomic methods. Material and methods. The chemoreactomic assessment of the pharmacological properties of pilim-1 and zinc derivatives of well-known NSAIDs (ketorolac, diclofenac, and nimesulide) was carried out using the methods of chemoinformatic analysis of molecules developed within the scientific school of Academician Yu.I. Zhuravlev. Results. Pilim-1 exhibits a distinct anti-inflammatory effect realized through modulation of cytokine activity as well as prostaglandin and leukotriene metabolism. A key distinguishing feature of the pilim-1 molecule is its neutrality with respect to vitamin metabolism while demonstrating a comparable anti-inflammatory potency to zinc-containing NSAID derivatives. The analgesic effect of pilim-1 is based on the inhibition of kinin and histamine receptors. The nociceptin receptor ORL1 can be inhibited by pilim-1 more effectively (IC50 198–214 nM) than zinc-NSAIDs (IC50 361–1093 nM). In the phenylquinone-induced writhing test in rats, pilim-1 demonstrated a slightly higher percentage of analgesia (44%; zinc-NSAIDs: 21–43%). The incidence of gastric ulcers at an oral dose of 100 mg/kg was estimated at 35% (compared to 75% with other molecules). Compared to other zinc-derived NSAID derivatives, pilim-1 exhibits minimal impact on vitamin and mineral metabolism. Conclusion. Chemoreactomic analysis of pilim-1 indicates promising prospects for its application as an anti-inflammatory drug.