α,ß-Didehydrosuberoylanilide hydroxamic acid (DDSAHA) as precursor and possible analogue of the anticancer drug SAHA

An alternate synthetic route to the important anticancer drug suberoylanilide hydroxamic acid (SAHA) from its α,ß-didehydro derivative is described. The didehydro derivative is obtained through a cross metathesis reaction between a suitable terminal alkene and N-benzyloxyacrylamide. Some of the didehydro derivatives of SAHA were preliminarily evaluated for anticancer activity towards HeLa cells. The administration of the analogues caused a significant decrease in the proliferation of HeLa cells. Furthermore, one of the analogues showed a maximum cytotoxicity with a minimum GI₅₀ value of 2.5 µg/mL and the generation of reactive oxygen species (ROS) as some apoptotic features.