A Structure–Activity Guided Strategy for Fluorescent Labeling of Annonaceous Acetogenin Mimetics and their Application in Cell Biology

Annonaceous acetogenins are a large family of fatty acid-derived natural products with unique structures. Many members in this diverse family have a broad spectrum of biological activities, the most impressive of which is anticancer activity. 2] ccording to the literature, acetogenins are believed to act ACHTUNGTRENNUNGdirectly at the terminal electron-transfer step in complex I of mitochondria. 4] However, despite studies to pinpoint the binding sites of acetogenins, the precise locations of the sites remain unclear due to a lack of detailed structural information about complex I. 4] Significant efforts have been made to uncover the cytotoxic mechanism of the natural acetogenins and their analogues. Our interest in modifying the natural acetogenins (e.g. , bullatacin) stems from the potent anticancer activ-