Synthesis of a New ent-Cyclozonarone Angular Analog, and Comparison of Its Cytotoxicity and Apoptotic Effects with ent-Cyclozonarone

Abstract

The synthesis of a newangular analog 11 of cyclozonarone was achieved via Diels-Alder reaction between a sesquiterpene-1,3-diene and 1,4-benzoquinone. The cytotoxic activity of ent-cyclozonarone [(+)-10] and the angular (−)-cyclozonarone analog 11 has been determined in three human cancer cell lines and in normal fibroblasts using the sulforhodamine B assay. The analyzed isomers induce cell death in different cancer cell lines by eliciting nuclear condensation and fragmentation, decreasing mitochondrial membrane permeability and increasing caspase-3 activity, all traits indicating apoptosis, with the effects of (+)-10 being stronger than those of 11 in all cases.

Keywords

• sesquiterpenequinone
• ent-cyclozonarone
• cancer cells
• cytotoxicity
• apoptosis
• caspase 3
• mitochondrial membrane permeability