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Background <p>A new series of <i>N</i>-(3-(1H-indol-5-yl) phenyl) (5a–5j) derivatives and <i>(4-(1H-indol-5-yl)piperazin-1-yl)(phenyl)methanone</i> (9a–9j) derivatives was designed and synthesized to explore their potential anti-inflammatory, analgesic, and ulcerogenic activities using established in vivo models. To further elucidate the interaction mechanisms and predict binding affinities, molecular docking studies were conducted for all the synthesized compounds using crystallographic structure of the human cyclooxygenase-2 (hCOX-2) enzyme. The docking scores were compared with rofecoxib, a well-known selective COX-2 inhibitor, serving as the reference standard. The study aimed to identify novel compounds with potent therapeutic efficacy and reduced gastrointestinal side effects.</p> Results <p>Compounds 5a–5j and 9a–9j were evaluated for anti-inflammatory activity using the carrageenan-induced paw edema model. Compounds showing significant anti-inflammatory effects were further assessed for analgesic and anti-ulcer activities. Among them, compounds 5f, 5j, 9e, and 9j exhibited notable binding affinities in molecular docking studies against hCOX-2, correlating well with their observed in vivo pharmacological activities. Compounds 5f and 5j emerged as the most potent candidates, demonstrating strong anti-inflammatory activity, significant analgesic effects, and excellent ulcer-protective properties. In contrast, compounds 9e and 9j showed moderate anti-inflammatory and analgesic activity. Remarkably, compounds 5f and 5j provided maximum protection against aspirin-induced gastric mucosal damage, with ulcer inhibition rates of 91.85 and 91.39%, respectively, compared to the standard anti-ulcer agent, ranitidine.</p> Conclusions <p>In the present study, the synthesized compounds were evaluated for their pharmacological effects using the carrageenan-induced paw edema method for anti-inflammatory activity, the hot plate method for analgesic activity, and the aspirin-induced ulcer model for anti-ulcer activity. Complementary molecular docking studies were performed to assess the binding affinities of the compounds to the hCOX-2 enzyme, and those with favorable docking scores were selected for in vivo evaluation. The results demonstrated that several synthesized compounds exhibited significant anti-inflammatory, analgesic, and anti-ulcer activities, highlighting their potential as therapeutic agents.</p> Graphical abstract <p></p>

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Synthesis and anti-inflammatory, analgesic, and anti-ulcerogenic bioevaluation of new indole bioconjugates

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月4日

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  • Savita Belwal,
  • Venkata Krishna Reddy,
  • Ram Bhavani,
  • Vasudha Bakshi

摘要

Background

A new series of N-(3-(1H-indol-5-yl) phenyl) (5a–5j) derivatives and (4-(1H-indol-5-yl)piperazin-1-yl)(phenyl)methanone (9a–9j) derivatives was designed and synthesized to explore their potential anti-inflammatory, analgesic, and ulcerogenic activities using established in vivo models. To further elucidate the interaction mechanisms and predict binding affinities, molecular docking studies were conducted for all the synthesized compounds using crystallographic structure of the human cyclooxygenase-2 (hCOX-2) enzyme. The docking scores were compared with rofecoxib, a well-known selective COX-2 inhibitor, serving as the reference standard. The study aimed to identify novel compounds with potent therapeutic efficacy and reduced gastrointestinal side effects.

Results

Compounds 5a–5j and 9a–9j were evaluated for anti-inflammatory activity using the carrageenan-induced paw edema model. Compounds showing significant anti-inflammatory effects were further assessed for analgesic and anti-ulcer activities. Among them, compounds 5f, 5j, 9e, and 9j exhibited notable binding affinities in molecular docking studies against hCOX-2, correlating well with their observed in vivo pharmacological activities. Compounds 5f and 5j emerged as the most potent candidates, demonstrating strong anti-inflammatory activity, significant analgesic effects, and excellent ulcer-protective properties. In contrast, compounds 9e and 9j showed moderate anti-inflammatory and analgesic activity. Remarkably, compounds 5f and 5j provided maximum protection against aspirin-induced gastric mucosal damage, with ulcer inhibition rates of 91.85 and 91.39%, respectively, compared to the standard anti-ulcer agent, ranitidine.

Conclusions

In the present study, the synthesized compounds were evaluated for their pharmacological effects using the carrageenan-induced paw edema method for anti-inflammatory activity, the hot plate method for analgesic activity, and the aspirin-induced ulcer model for anti-ulcer activity. Complementary molecular docking studies were performed to assess the binding affinities of the compounds to the hCOX-2 enzyme, and those with favorable docking scores were selected for in vivo evaluation. The results demonstrated that several synthesized compounds exhibited significant anti-inflammatory, analgesic, and anti-ulcer activities, highlighting their potential as therapeutic agents.

Graphical abstract