Get started
Work

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

Year: 2025
Type: article
Abstract: 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.
DOI: 10.17749/2070-4909/farmakoekonomika.2025.280
Authors: P. A. Galenko-Yaroshevsky, I. Y. Torshin, A. N. Gromov, I. A. Reyer, O. A. Gromova, B. A. Trofimov, L. N. Parshina, R. A. Murashko, O. V. Shelemekh, A. V. Zadorozhniy, V. L. Popkov, A. V. Zelenskaya, I. B. Nektarevskaya, A. V. Sergeeva, A. V. Uvarov, Yu. V. Tovkach, I. V. Sholl
Language: English
Subfield: Pharmacology
Field: Medicine
Open Access status: gold
Estimated APC paid: $142
OpenAlex ID: W4410016410
FWCI:
Cites: 31
Cited by:
Related to: 10