Remarkable substituent effect:: β-aminosquamocin, a potent dual inhibitor of mitochondrial complexes I and III

The introduction of a primary amine function on the terminal alpha,beta-unsaturated lactone of squamocin 1, a common structural hallmark of annonaceous acetogenins, shifted this specific inhibitor of mitochondrial complex I into a potent dual inhibitor of complexes I and III. The mechanism of action of beta-aminosquamocin 2, against these two respiratory targets, is studied and discussed in view of current structure-activity relationship knowledge in the acetogenin series. (c) 2005 Elsevier B.V. All rights reserved.