Synthesis and Bioactivity of Furoxanthone Derivatives

The linearly and angularly isomeric furoxanthones 3a, 3b were synthesized by etherification and cyclization of 1,3-dihydroxylxanthone, which was synthesized from salicylic acid and phloroglucinol; then ten furoxanthone derivatives 4 and 5 were prepared via Mannich reaction of 3a, 3b, respectively, finally the ten corresponding quaternary ammonium salts 6 and 7 were obtained by quaternization of 4 and 5; the structures of the synthesized compounds were confirmed by IR, NMR, MS and elemental analysis. Acetylcholinesterase (AChE) inhibitory activities of compounds 4 similar to 7 and anti-cancer activities of compounds 6, 7 were also investigated. The results indicated that compounds 4 similar to 7 were capable of inhibiting AChE in vitro with moderate to good activities, IC50=2.0 similar to 12.4 mu mol/L. MTT assay indicated that compounds 6, 7 possessed effectively inhibitory activity against the proliferation of four cancer cells, including HepG2 (liver cancer), SPC-A (lung cancer), KB (oral epithelial carcinoma) and MCF-7 (galactophore cancer), among which 6c against HepG2 and 7d against MCF-7 had the highest inhibitory activities, with the IC50 being 0.82 and 0.77 mu mol/L, respectively.