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

Abstract

C-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.