6-Hydroxy-benzofuran-3-(2H)-ones as Potential Anti-Inflammatory Agents:Synthesis and Inhibitory Activity of LPS-Stimulated ROS Production in RAW 264.7 Macrophage

摘要

Reactive oxygen species(ROS)are oxygen containing chemical reactive molecules,which are considered as a factor in the inflammatory responses induced by lipopolysac-charide(LPS).1 LPSs are the exotoxins that activate macrophages to liberate inflammatory cytokines including interleukin-1 beta(IL-1),tumor necrosis factor(TNF),nitric oxide(NO),and prostaglandin E2(PGE2).The pathophysiological processes of various inflammatory diseases are mediated by these cytokines.Aurones are structural isomers of flavones,which are biosynthesized from chalcones by auresidin synthase.3 These possess not only anticancer,antiparasitic,antimicrobial,antiviral properties but also antiinflammatory property.4 It is reported that the anti-inflammatory activity of chalcone derivatives is accelerated by the incorportaion of electron withdrawing groups like flourine,chorine in the chalcone moiety.Previously our group also reported significance of halogens on inhibitory effect of LPS-stimulated ROS production in RAW 264.7 macrophages.It is further reported that the position and electronic nature of the substituent on ring B of aurone scaffold affect the potency,selectivity,and cytotoxicity of the compounds.7 The importance of hydroxyl group in benzofuran-3-(2//)-one moiety is highlighted in the bioassay of naturally occurring aurones such as aureusidin,sulfuretin,and maritimetin.8'9 Among chalcones,flavones and aurones,there have been few studies on aurones and its antiinfammatory activity.