Epoxy-acetogenins and other polyketide epoxy derivatives as inhibitors of the mitochondrial respiratory chain complex I

Annonaceous acetogenins (ACG), an extensive group of cytotoxic natural prod ucts, are antitumor agents whose main mode of action is inhibition of the m ammalian mitochondrial complex I. Herein we describe the importance of the different chemical groups along the alkyl chain for optimal inhibitory pote ncy, discussing the structurally relevant factors present in these compound s. For this purpose, a series of epoxide derivatives from alpha-linolenic a cid were prepared and their activity compared with that of epoxy-acetogenin s and tetrahydrofuranic (THF) acetogenins isolated from Rollinia membranace a.