Synthesis and Biological Evaluation ofPyrano[2,3-f]chromene-4,8-dione Derivatives as Potential Anticancer Agents

Based on the hit 5-hydroxy-2-methyl-10-propyl-2,3-dihydro-4H,8H-pyrano[2,3-j]chromene-4,8-dione（1）, a series of pyrano[2,3-f]chromene-4,8-dione derivatives was designed and synthesized using pb_loroghicinol as startingmaterial. Meanwhile, a regioselective synthetic route was developed for 5-methoxy-2,3-dihydro-4H,8H-pyrano-[2,3-f]chromene-4,8-dione products（11a-11f）, and their structures were further confirmed by nuclear Overhausereffect（NOE）. The evaluation of anticancer activities of these compounds against four human cancer cell lines,including human glioma cell line （SHG-44）, human lung cancer cell line（H1299）, breast cancer cell line（/vICF7） andhuman colon carcinoma cell line（HCT-116） in vitro shows that 5-methoxy-2,2-dimethyl-9-chloro-10-trifluormethyl-2,3-dihydro-4H,8H-pyrano[2,3-f]chromene-4,8-dione（lle） possesses the best anticancer activities with IC50 values of6.68, 7.90, 5.16 and 4.82 gmol/L, respectively. Finally, the preliminary structure-activity relationships（SARs） weresttmmarized, which could pave the way for generating more potent anticancer agents with drug-like properties.