Anhydride modified cantharidin analogues: Synthesis, inhibition of proteinphosphatases 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 C olon 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 PP2 A selectivity (ca. 5- to 20-fold) and inhibition typically in the low mu M range (comparable, in some cases to cantharidin). The anticancer activity o f these analogues varied with the cell line under study; however, many of t hem showed selective cytotoxicity for the colon tumour cell lines. (C) 2000 Elsevier Science Ltd. All rights reserved.