Synthesis, characterization, and anti‐inflammatory properties of novel ethyl 3‐benzoyl‐7‐(trifluoromethyl)indolizine‐1‐carboxylate derivatives: In silico and in vitro analysis

Abstract

AbstractSeries of 7‐(Trifluoromethyl) substituted indolizine 4a‐g was synthesized using the one‐pot method. Spectroscopic techniques such as IR, 1H‐NMR, 13C‐NMR, and HRMS were used for the structure confirmation of newly synthesized compounds. These 4a‐g compounds were tested for their anti‐inflammatory activity. In this study, we identified novel indolizine derivative compounds 4a‐g selectively targeting COX‐2 enzyme, tumor necrosis factor‐α (TNF‐α) and, interleukin‐6 (IL‐6). The in silico docking studies of 4a‐g showed that these compounds have a higher affinity for COX‐2 enzyme, TNF‐ α, and IL‐6. In silico ADME profile analysis predicts that these compounds have good gastrointestinal tract and blood–brain barrier absorption. In vitro studies showed that compound 4d significantly reduces the level of COX‐2 enzymes as compared to indomethacin. Compounds 4e, 4f, and 4a were also found to significantly reduce the level of TNF‐α, while compounds 4f, 4g, and 4d, showed a reduction in the level of IL‐6 when compared to indomethacin. Compounds 4a, 4d, and 4f also reduces nitric oxide (NO) level, compared to indomethacin. Overall, the current study illustrates significant anti‐inflammatory activities of these novel 7‐(Trifluoromethyl) substituted indolizine derivatives.