Abstract:

To introduce the imidazole ring to the bromo-methoxyl benzophenone structures and find the target compounds with high protective activity on vacular endothelium cells, eight novel bromo-methoxyl benzophenone imidazole compounds were synthesized using 5-bromo-2-methylbenzoic acid as starting material via following reactions:acylating chlorination, Friedel acylation, bromination, radical substitution with N-bromosuccinimide(NBS) and nucleophilic substitution with substituted imidazoles. The structures of the target compounds were confirmed by proton and carbon nuclear magnetic resonance spectroscopy(¹H and ¹³C NMR) and high resolution mass spectrometry(HRMS). Additionally, the protective effects of the target compounds against H₂O₂-induced EA.hy 926 cells injury were evaluated by methylthiazolyldiphenyl-tetrazolium bromide(MTT) assay and their structure-activity relationships were also preliminarily discussed. The in vitro results show that target compounds 6a, 6g and 6h exhibit significant cytoprotective activities and their half maximal inhibitory concentration(EC₅₀) values are 1.9, 4.0 and 3.2 μmol/L, respectively, superior to the positive control Quercetin(EC₅₀≈18 μmol/L). These results also suggest the potential application prospect of target compounds in the treatment of cardiovascular diseases.

Key words: bromo-methoxyl benzophenone, imidazole, EA.hy 926 cells, protective activity