Design, synthesis and anticancer activity of novel dihydrobenzofuro[4,5-b] [1,8]naphthyridin-6-one derivatives

Article abstract of DOI:10.1016/j.bmcl.2011.08.016

On the basis of the chemical structures of psorospermin with a xanthone template and acronycine derivatives with an acridone template, rac-1 and rac-2 constructed on an 1,2-dihydrobenzofuro[4,5-b][1,8]naphthyridin-6(11H)-one scaffold were designed and synthesized as potential anticancer agents. Their anticancer activities were evaluated against five human cancer cell lines. Rac-2 showed similar anticancer activity to doxorubicin and rac-1 exhibited even higher anticancer activity against LNCaP (IC₅₀ = 0.14 μM), DU145 (IC₅₀ = 0.15 μM), PC3 (IC₅₀ = 0.30 μM) and MCF-7 (IC₅₀ = 0.26 μM) cancer lines than doxorubicin and rac-2. Also, rac-1 revealed very potent anticancer activity (IC₅₀ = 0.15 μM) against MCF-7/ADR cell (doxorubicin-resistant breast cancer cell) lines and induced G2/M phase arrest of the cell cycle in MCF-7/ADR cells.