N 5 (196) 2025. P. 90–95

PHARMACOLOGICAL ACTIVITY OF 2-(DIETHYLAMINO)ETHYL-4-[(11-OXOINDENE[2,1-B] QUINOXALINE-6-CARBONYL)AMINO]BENZOATE DURING TRANSDERMAL APPLICATION

L. V. Eberle, K. D. Sazonov, Ya. V. Rozhkovskyi, S. I. Bohatu, B. V. Prystupa

Odesa National Medical University, Odesa, Ukraine,
Odesa I. I. Mechnikov National University, Odesa, Ukraine

DOI 10.32782/2226-2008-2025-5-15

In medical practice, pain syndrome and inflammation are common clinical manifestations that significantly reduce the quality of life of patients. A promising direction of modern pharmacotherapy is the development and search for local dosage forms with analgesic and anti-inflammatory effects.

The aim of this work was to study the analgesic and anti-inflammatory activity of a new compound – 2-(diethylamino)ethyl-4-[(11-oxoindeno[2,1-b]quinoxaline-6-carbonyl)amino]benzoate in the composition of ointments of different concentrations.

The study was conducted on 50 rats and 60 mice, in accordance with the requirements of GLP and ethical standards. The study of analgesic activity was carried out on models of thermal (“hot water”) and chemical (allyl isothiocyanate test) pain. The assessment of anti-inflammatory activity was carried out on models of exudative inflammation induced by trypsin and zymosan.

Research results. According to the results of the study, in the “hot water” test, 5% ointment based on 2-(diethylamino)ethyl-4-[(11-oxoindeno[2,1-b]quinoxaline-6-carbonyl)amino]benzoate provided a significant reduction in pain sensitivity by 63.8%, and in the allyl isothiocyanate test — 88 to 66.5% compared to the control group, which indicates a pronounced analgesic activity of the studied compound. In the model of inflammation induced by zymosan, a moderate anti-exudative effect was established, which was manifested by a decrease in the inflammatory reaction by 27.4%, while in the trypsin model no significant effect was recorded.

Thus, it was established that the studied compound is characterized by pronounced local analgesic activity and limited anti-inflammatory properties, which depend on the type of model. The obtained results indicate the feasibility of further preclinical studies of the drug as a potential local analgesic with a combined mechanism of action.

Keywords: analgesic activity, antiexudative activity, indenoquinoxoline derivatives, 2-(diethylamino)ethyl-4-[(11-oxoindeno[2,1-b] quinoxaline-6-carbonyl)amino]benzoate.

REFERENCES

  1. Соhen SP, Vase L, Hooten WM. Chronic pain: an update on burden, best practices, and new advances. 2021; 397: 2082–2097. https://doi.org/10.1016/s0140-6736(21)00393-7.
  2. Wilson JM, Schreiber KL, Mackey S, et al. Increased pain catastrophizing longitudinally predicts worsened pain severity and interference in patients with chronic pain and cancer: A collaborative health outcomes information registry study. Psychooncology. 2022 Aug; 31(10): 1753–1761. https://doi.org/10.1002/pon.6020.
  3. Tom AA, Rajkumar E, John R, George AJ. Determinants of quality of life in individuals with chronic low back pain: a systematic review. Health Psychology and Behavioral Medicine. 2022 Feb; 10(1): 124–144. DOI: 10.1080/21642850.2021. 2022487.
  4. Abd El Salam HA, El-Bendary MA, Ibrahim M, El-Samahy FA. Synthesis, Molecular Modeling and Biological Evaluation of Indeno[1,2-b]quinoxaline Derivatives as Antifungal and Antibacterial Agents. Egyptian Journal of Chemistry. 2020; 63(7): 2577–2590. https://doi.org/10.21608/ejchem.2020.21366.2275.
  5. Eldeken GA, El-Samahy FA, Zayed, EM, Osman FH, Elgemeie GE. Synthesis, Biological Activities and Molecular Docking Analysis of a Novel Series of 11H-Indeno[1,2-b]quinoxalin-11-one Derivatives. Mol. Struct. 2022 Aug; 1261: 132929. https://doi.org/10.1016/j.molstruc.2022.132929.
  6. Sazonov KD, Ishkov YuV, Shevchenko OV. Synthesis of new derivatives of indenoquinoxalinecarboxylic acids with amines and in silico prediction of their biological activity. Visnyk Odeskoho natsionalnoho universytetu. Khimiia. 2024; 1(87): 91–98. https://doi.org/10.32434/0321-4095-2024-157-6-40-46.
  7. Demchenko SA, Fedchenkova YA, Tsyhankov SA, et al. The synthesis, analgesic and anti-inflammatory activity of 3-aryl(heteryl)-2-(6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepin-3-yl)-acrylonitrile derivatives. Journal of Organic and Pharmaceutical Chemistry. 2020; 18(2): 32–39. https://doi.org/10.24959/ophcj.20.193511.
  8. Zygmunt M, Ślusarczyk M, Jankowska A, et al. Evaluation of analgesic and anti-inflammatory activity of purine-2,6-dione-based TRPA1 antagonists with PDE4/7 inhibitory activity. Pharmacological Reports. 2022; 74(5): 982–997. https://doi.org/ 10.1007/s43440-022-00397-6.
  9. Zakon Ukrainy “Pro zakhyst tvaryn vid zhorstokoho povodzhennia” [Law of Ukraine “On Protection of Animals from Cruelty”] vid 21.02.2017 № 2229-VIII. Vidomosti Verkhovnoi Rady Ukrainy. 2017; № 24: 131. (In Ukrainian). https:// zakon.rada.gov.ua/laws/show/3447-15.
  10. Percie du Sert N, Hurst V, Ahluwalia A, et al. ARRIVE Guidelines 2.0: Updated guidelines for reporting animal research. PLOS Biology. 2020; 18(7): e3000410. https://doi.org/10.1371/journal.pbio.3000410.
  11. Eberle LV, Kobernik AO, Kravchenko IA. Analhetychna aktyvnist hustoho ekstraktu imbyru (Zingiber officinale). Zhurnal Aktualni problemy transportnoi medytsyny. 2017; 4(50): 120–125. (In Ukrainian). https://www.researchgate.net/ publication/325825281.
  12. Pakale PV, Khanwelkar C, Thorat V, Jadhav S, Tiwari DD. Study of the Analgesic Activity of the Aqueous and Methanolic Extracts of Fresh Rhizome of Zingiber officinale in Wistar Rats. Cureus. 2024; 16(11): e74219. https://doi.org/10.7759/ cureus.74219.
  13. Nefyodov OO, Eberle LV, Tsisak AO, et al. Evaluation of the antinociceptive and antiexudative effects of a complex herbal preparation in the therapy of somatic pain and inflammation of various genesis. World of Medicine and Biology. 2023; 3(85): 224–229. http://dx.doi.org/10.26724/2079-8334-2023-3-85-224-229.
  14. Aleksandrova AI, Hrytsuk OI, Eberle LV, Radayeva IM, Ustyanska OV, Tsisak AO. Protyzapalna ta analhetychna diia mazi, yaka mistyt karotynoidy heksanovoho ekstraktu Cladophora aegagropila. Visnyk Vinnytskoho natsionalnoho medychnoho universytetu. 2024; 28(1): 17–22. (In Ukrainian). https://doi.org/10.31393/reports-vnmedical-2024-28(1)-03.
  15. Stefanov OV. Doklinichni doslidzhennia likarskykh zasobiv: metodychni rekomendatsii. [Preclinical research of medicines: method. Recommendations]. Kyiv: Avytsena; 2001. 528 p. (in Ukrainian). https://zenodo.org/records/8139960.
  16. Zakon Ukrainy “Pro zakhyst tvaryn vid zhorstokoho povodzhennia” vid 21 liutoho 2006 roku No 3447-IV. Vidomosti Verkhovnoi Rady Ukrainy. 2006; 27: St. 230. (In Ukrainian). https://npu.gov.ua/acts/pro-zahist-tvarin-vid-zhorstokogo-povodzhennya?
  17. Le Bars D, Gozariu M, Cadden SW. Animal models of nociception. Pharmacological Reviews. 2001; 53(4): 597–652. https://doi.org/10.1124/pr.53.4.597.
  18. Singh D, Parle M, Dhingra S. Evaluation of the analgesic effect of morphine on models of acute nociceptive pain in rats with a central noradrenergic system lesion. Pharmacology Biochemistry and Behavior. 2016; 150–151: 42–48. https://doi.org/ 10.1016/j.pbb.2016.08.001.
  19. Guerrero-Alba R, Méndez-Díaz M. Animal models to study nociception induced by chemical irritants acting on TRP channels: An overview. Frontiers in Pharmacology. 2020; 11: 575250. https://doi.org/10.3389/fphar.2020.575250.
  20. Sałat K, Filipek B. Antinociceptive activity of transient receptor potential channel TRPV1, TRPA1, and TRPM8 antagonists in neurogenic and neuropathic pain models in mice. Journal of Zhejiang University Science B. 2015; 16(3): 167–178. https:// doi.org/10.1631/jzus.B1400189.
View article PDF