Anhydride modified cantharidin analogues: synthesis, inhibition of protein phosphatases 1 and 2A and anticancer activity

Two series of anhydride modified cantharidin analogues were synthesised and screened for their Phosphatase inhibition (PP1 and PP2A) and cytotoxicity in various Cancer cell lines (Ovarian A2780, ADDP; Osteosarcoma 143B; and Colon HCT116 and HT29). One series was synthesised by a novel, high yielding one-pot hydrogenation-ring-opening-esterification procedure, the Other by acid catalysed acetal formation. Analogues 5-7 and 9 displayed moderate PP2A selectivity (CA. 5- to 20-fold) and inhibition typically in the low microM range (comparable, in some cases to cantharidin). The Anticancer activity of these analogues varied with the cell line under study; however, many of them showed selective cytotoxicity for the colon tumour cell lines.