Synthesis and pharmacological activities of 4-aryl-3,4-dihydrocoumarin derivatives

4-Aryl-3,4-dihydrocoumarins(neoflavones) represent a minor class of natural compounds which based on the C6—C3—C6 skeleton with an characteristic aryl group in the 4 position.Structurally,4-aryl-3,4-dihydrocoumarins can also be regarded as the hybrids of isoflavones and coumarins,thus being expected to possess corresponding bioactivity.In this paper,ten 4-aryl-3,4-dihydrocoumarins were synthesized by two steps.The first condensation of substituted benzaldehydes and malonic acids in the presence of pyridine and piperidine at 70-90 ℃ gave the expected cinnamic acids in good yields.Then condensation of substituted cinnamic acids with appropriate phenols in the presence of BF3-Et2O and POCl3 gave the target molecule at room temperature.Their structures were confirmed by EI-MS,IR and 1H-NMR.The antioxidant and antitumor activity of these compounds were evaluated by DPPH and MTT assay,respectively.Some of 4-aryl-3,4-dihydrocoumarin derivatives showed strong scavenging activities against 1,1-diphenyl-2-picrylhydrazyl radical:(±)-7,8-dihydroxy-4-(3-hydroxy-4-methoxyphenyl)-3,4-dihydrocoumarin(3c) EC50=(2.69±0.09) μmol · L-1,(±)-7,8-dihydroxy-4-(4-methoxyphenyl)-3,4-dihydrocoumarin(3g) EC50=(2.32±0.10) μmol · L-1 and weak antitumor in vitro activity against BGC-823 cell line[(±)-7,8-dihydroxy-4-(3-hydroxy-4-methoxyphenyl)-3,4-dihydrocoumarin(3c) IC50=(136±21) μmol · L-1].The results showed that the 4-arylcoumarins which possessing the catechol moiety may be a beneficial scaffold for therapeutic purpose.