Design, synthesis, and evaluation of novel indomethacin–antioxidant codrugs as gastrosparing NSAIDs

Abstract

Indomethacin has been conjugated with different antioxidants having antiulcerogenic activity with the objective of obtaining indomethacin-antioxidant codrugs as gastrosparing NSAIDs devoid of ulcerogenic side effects. Purified synthesized codrugs have been characterized by m.p., TLC, elemental analyses, FTIR, NMR, MS. The synthesized derivatives have been screened for their antiinflammatory, analgesic, and antiulcer activity. The codrugs showed retention of antiinflammatory activity with reduced ulcerogenic side effects. These results indicated that indomethacin-antioxidant codrugs have the potential to be developed as gastrosparing NSAIDs.

Tailored Functionalization of Natural Phenols to Improve Biological Activity

“…Promising results have also been achieved with the conjugation of nonsteroidal anti-inflammatory drugs (NSAIDs) to thymol, to prevent adverse gastrointestinal mucosal reactions, which are typical side effects related with long-term use of NSAIDs [ 137 , 138 , 139 , 140 ]. The formation of gastric ulceration related with NSAID therapy is usually due to the local generation of reactive oxygen species (ROS); thus, the introduction of antioxidant components in NSAIDs’ structure can limit such undesired effects.…”

Synthesis and in vivo evaluation of pyrazoline-thiazolidin-4-one hybrid Les-5581 as a potential non-steroidal anti-inflammatory agent

“…New small molecules as modern anti-inflammatory agents with synergic action and minimizing toxicity were developed using molecular hybridization and multiple-ligand drugs techniques [7,8]. The combination of anti-oxidative and anti-inflammatory scaffolds in one molecule was shown to be a promising strategy for the search, further optimization and development of new hits/leads/candidates as potent and safe NSAIDs [8,9]. The study of hybridization of potential scaffolds with both antioxidant and anti-inflammatory properties is of particular interest.…”