Synthesis and antiproliferative activities of polymethoxyflavones aminoalkyl and amino acid derivatives

Twelve novel aminoalkyl derivatives 3a-3f, 4a-4f and four novel amino acid derivatives 5a, 5b, 6a and 6b of polymethoxyflavones 1 and 2 were synthesized through regioselective demethylation, etherification, amination, EDC1-mediated amide condensation and alkaline hydrolysis, using tangeretin and nobiletin as starting materials. Their antiproliferative activities against four different human cancer cell lines (Aspc-1, SUN5, HepG-2 and HCT116) were evaluated by in vitro CCK-8 assay. The results show that the majority of the synthetic compounds exhibited moderate to good antiproliferative activity. In particular, the antiproliferative activity of compound 5b against HepG-2 cells (IC50 0.057 mu M) was equal to the positive control drug Staurosporine (IC50 0.0575 mu M).