Facile Preparation of 2-Arylbenzo[b]furan Molecules and Their Anti-inflammatory Effects

Abstract

An efficient and practical preparation of 2-arylbenzo[b]furan molecules including natural egonol, XH-14, ailanthoidol, and unnatural derivatives is demonstrated using Sonogashira coupling, iodine induced cyclization and Wittig reaction. Anti-inflammatory effects of the prepared benzo[b]furans were examined in lipopolysaccharide (LPS)-stimulated RAW 264-7 macrophages. The results showed that ailanthoidol, XH-14 and three other unnatural derivatives (9-10, 13) inhibited significantly the production of inflammatory mediator nitric oxide without showing cytotoxicity.

<p>Recent Updates on Anti-Inflammatory and Antimicrobial Effects of Furan Natural Derivatives</p>

“…Furthermore, ailanthoidol was the most anti-inflammatory compound with a unique possibility to inhibit nitric oxide (NO) production at 10 µM. 24 Furthermore, Park et al investigated the anti-inflammatory effects of XH-14, isolated from Salvia miltiorrhiza, and revealed that this compound can inhibit LPS-induced NO production in a dose-dependent manner most probably via a reduction in iNOS protein expression. 25 They also noticed that PGE2 was decreased after the exposure to XH-14.…”

“…Also, these molecules can inhibit NF-κB and MAPKs pathways. 24,95 Moreover, two aromatic rings on the furanone skeleton enhance the lipophilicity of these compounds which enhance its antioxidative and anti-inflammatory effects. Taken all together, it is expected that the presence of enol and phenol moieties in furanones could induce free radical scavenger activity and related effects.…”

Synthesis of New 2-Arylbenzo[b]furan Derivatives via Palladium-Catalyzed Suzuki Cross-Coupling Reactions in Aqueous Media

“…Meanwhile, 5-(3-hydroxypropyl-7-methoxy-2-(3′-methoxy-4′-hydroxyphenyl)benzo[ b ]furan-3-carbaldehyde (XH-14) ( Figure 1 , 2 ), which has been widely used in China for the treatment of coronary heart diseases such as myocardial infarction and angina pectoris [ 18 ], was isolated from the plant Salvia miltorrhiza Bunge (Chinese name “Danshen”). Jun [ 19 ] obtained three XH-14 analogues whose anti-inflammatory effects were examined in lipopolysaccharide(LPS)-stimulated RAW 264-7 macrophages. The results showed that three structurally modified derivatives ( Figure 1 , 3a – 3c ) inhibited significantly the production of inflammatory mediator nitric oxide without showing cytotoxicity.…”

Ailanthoidol suppresses lipopolysaccharide-stimulated inflammatory reactions in RAW264.7 cells and endotoxin shock in mice

“…Ailanthoidol was synthesized from vanillin in five steps as previously reported [Hwang et al, 2010]. LPS and fluorescein isothiocyanate (FITC)-conjugated LPS derived from Escherichia coli (0111:B4) were obtained from Sigma-Aldrich (St, Louis, MO).…”