Analgesic and Anti-Inflammatory Potential of Indole Derivatives

Rudrapal M., ÇELİK İ., Chinnam S., Cevik U., Tallei T. E., Nizam A., ...More

POLYCYCLIC AROMATIC COMPOUNDS, vol.43, no.9, pp.7732-7753, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 43 Issue: 9
  • Publication Date: 2023
  • Doi Number: 10.1080/10406638.2022.2139733
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, Applied Science & Technology Source, CAB Abstracts, Chemical Abstracts Core, Communication Abstracts, Food Science & Technology Abstracts, Metadex, Pollution Abstracts, Veterinary Science Database, Civil Engineering Abstracts
  • Page Numbers: pp.7732-7753
  • Keywords: Analgesic, anti-inflammatory, indole, molecular docking, molecular dynamics, ADME prediction, BIOLOGICAL EVALUATION, MOLECULAR-DYNAMICS, IN-SILICO, DOCKING, DISCOVERY, DESIGN, AGENTS, VITRO, TOOL
  • Anadolu University Affiliated: Yes


Some indole analogues show a good analgesic activity but on the other hand, it has some serious side effects like gastric ulcer. Therefore, there is still a need to develop derivatives of non-steroidal anti-inflammatory drugs (NSAIDs) with fewer side effects. For this purpose, some indole derivatives were prepared with objectives to develop new derivatives with maximum efficacy and minimum side effects. 1-(1H-indol-1-yl)-2-(substituephenoxy)-ethan-1-one derivatives (M1-M4) were analyzed further by thin-layer chromatorgarphy (TLC), melting point, IR, and H-1-NMR. The synthesized compounds then underwent oral toxicity studies that include hematological, biochemical, and histopathological findings. The compound was then evaluated for in vivo anti-inflammatory and analgesic activities on carrageenan-induced rat paw edema and acetic acid-induced writhing methods. As a result of the biological activities, promising results were obtained in the compound M2 (2-(2-aminophenoxy)-1-(1H-indol-1-yl)ethanone) and it was subjected to further studies. It was found that compound M2 was practically nontoxic, and no clinical abnormalities were found in hematology and biochemistry, correlated with histopathological observation. It also showed significant anti-inflammatory and analgesic activities at its oral high dose (400 mg/kg). The study suggested that compound M2 was found to have significant anti-inflammatory and analgesic activities. The possible mechanism of M2 might suggest being act as a central anti-nociceptive agent and peripheral inhibitor of painful inflammation. The possible mechanism of action of the compounds whose biological activity was evaluated was explained by molecular docking study against COX-1 and COX-2, and the most active compound M2 formed -9.3 and -8.3 binding energies against COX-1 and COX-2. In addition, molecular dynamics (MD) simulation of both M2's complexes with COX-1 and COX-2 was performed to examine the stability and behavior of the molecular docking pose, and the MM-PBSA binding free energies were measured as -153.820 +/- 11.782 and -172.604 +/- 9.591, respectively. Based on computational ADME studies, compounds comply with the limiting guidelines.