Synthesis and Anti-inflammatory Effect of Simple 2,3-Diarylindoles. On Route to New NSAID Scaffolds

Nitrogen-containing drugs represent one of the worldwide most extensive sources of treatments for different diseases. Indomethacin as example, is one of the most important non-steroidal anti-inflammatories (NSAID) indol-containing drug. Its relevance has been demonstrated the last 50 years with excellent pharmacological results. Its efficacy as an anti-inflammatory treatment, inspired us the exploration of indol-containing structurally less elaborated compounds which kept and/or improve the anti-inflammatory activity compared with indomethacin. Herein is summarized and discussed our initial findings on the synthesis and anti-inflammatory effect of different 2,3-diarylindoles, designed for strategically favoring the plausible and selective interactions with COX-2, on route to new simple NSAID scaffolds. The TPA model and formalin test were used in this study to generate inflammation in mice for conducting the assays with the synthesized 2,3-diarylindoles. Docking analysis revealed stronger N-H indolic interactions with COX-2 for 6-methoxy-2-phenyl-3-(4-chlorophenyl)-1H-indole, one of the most active of the synthesized compounds when compared with indomethacin. This, experimentally match with the anti-inflammatory observed effect and putatively indicates the biochemical action mechanism. The design, synthesis, and biological evaluation of 2,3-diarylindoles as structural simple scaffold is described as potential non-steroidal anti-inflammatories (NSAID) candidates. The TPA model as well as formalin test revealed comparable and, in some cases, better activity as well as stronger NH-COX2 interactions than extensively prescribed indomethacin. Docking analysis postulate COX-2 as their action site. image