Synthesis and cytotoxic evaluation of protoanemonin and three brominated derivatives

Abstract

The protoanemonin, a natural furanone, was synthesized from (Z)-4-bromo-5-(bromomethylene)-furan-2(5H)-one by a reductive dehalogenation reaction with zinc. The 5-(dibromomethylene)-2(5H)-furanone and (E)-5-(bromomethylene)-2(5H)-furanone were also synthetized from levulinic acid bromination and acid promoted cyclization. The antiproliferative activity of all synthesized compounds against the human cancer cell lines PC-3 (prostate) and U-251 (glioblastoma) was investigated. The results showed that all the obtained furanones are more active than the reference drug cisplatin, with IC50 values in the range of 0.31 ± 0.02 to 7.30 ± 0.08 μM. However, (E)-5-(bromomethylene)-2(5H)-furanone, with a bromine atom in the double bond, was the most active, and demonstrated to be about 25-fold more active than the reference drug cisplatin.