Synthesis and antiproliferative activities of polymethoxyflavones aminoalkyl and amino acid derivatives

Twelve novel aminoalkyl derivatives3a-3f,4a-4fand four novel amino acid derivatives5a,5b,6aand6bof polymethoxyflavones1and2were synthesized through regioselective demethylation, etherification, amination, EDCl-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 byin vitroCCK-8 assay. The results show that the majority of the synthetic compounds exhibited moderate to good antiproliferative activity. In particular, the antiproliferative activity of compound5bagainst HepG-2 cells (IC₅₀0.057 μM) was equal to the positive control drug Staurosporine (IC₅₀0.0575 μM).