title: Pharmacological evaluation of 9,10-dihydrochromeno[8,7-e][1,3]oxazin-2(8H)-one derivatives as potent anti-inflammatory agent.
abstract: 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 6.25μg/ml and 25μg/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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin, 133002, China.
authors.forename: Hong-Jian
authors.initials: HJ
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin, 133002, China.
authors.forename: Yan-Fei
authors.initials: YF
authors.lastname: Li
authors.affiliation: Department of Pathology, 306 Hospital of PLA, Beijing, 100101, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Cao
authors.affiliation: Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin, 133002, China. Electronic address: ystian@ybu.edu.cn.
authors.forename: Yu-Shun
authors.initials: YS
authors.lastname: Tian
authors.affiliation: Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin, 133002, China. Electronic address: zsquan@ybu.edu.cn.
authors.forename: Zhe-Shan
authors.initials: ZS
authors.lastname: Quan
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D010078:Oxazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D003374:Coumarins; D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D010078:Oxazines; D014409:Tumor Necrosis Factor-alpha
keywords: Coumarin; MAPKs; Mannich reaction; Molecular docking; NF-κB; Synthesis