Pharmacological evaluation of 9,10-dihydrochromeno[8,7-e][1,3]oxazin-2(8H)-one derivatives as potent anti-inflammatory agent

Background non-steroidal anti-inflammatory drugs (nsaids) are the most widely administered drugs for the treatment of inflammation. however,they usually cause some unexpected side effects. coumarins and their derivatives exhibit broad-spectrum biological activities. in order to develop new anti-inflammatory drugs with high anti-inflammatory activity and less side effects,a series of 9-substituted-9,10-dihydrochromeno[8,7-e][1,3]oxazin-2(8h)-one derivatives were designed,synthesized,and screened for their anti-inflammatory activities. methods we investigated the effect of compound 9-(2-chlorophenyl)-9,10-dihydrochromeno[8,7-e][1,3]oxazin-2(8h)-one (b3) on lipopolysaccharide (lps)-induced cytokine levels in raw 264.7 cells at concentrations between 6.25 μg/ml and 25 μg/ml. concentrations of tumor necrosis factor-α (tnf-α) and interleukin-6 (il-6) were measured by enzyme-linked immunosorbent assay (elisa). moreover,mitogen-activated protein kinase (mapk) and nuclear factor-κb (nf-κb) activation was investigated by western blot assay. results compound b3 could inhibit inflammatory responses via suppression of the nf-κb and mapk signaling pathways. docking study of the prepared compounds was performed for the study of interaction of molecules with the active site of tnf-α. conclusion 9,10-dihydrochromeno[8,7-e][1,3]oxazin-2(8h)-one derivatives showed anti-inflammatory activity. compound b3 was the most potent. the results of this study are encouraging further investigations to develop compound b3 as a novel therapeutic agent for inflammatory disorders. © 2016 institute of pharmacology,polish academy of sciences