Annonaceous Acetogenins as Model of Bioactive Heterocyclic Derivative Structures: Extraction and Biological Evaluation

Abstract

Most annonaceous acetogenins are characterized by an unbranched C32 or C34 fatty acid ending in a γ-lactone, with a long alkyl chain that usually presents hydroxyls groups, tetrahydrofurans and tetrahydropyrans. While many studies have addressed the properties and synthesis of natural acetogenins due to their attractive biological activities, a number of analogues have also been described. This review covers the isolation, and biological evaluation of acetogenins. These compounds represent a class of bioactive compounds whose cytotoxicity seems to be related to the conformation adopted in the membrane revealed by the intermolecular interactions between the headgroups of membrane (specifically phosphate groups) and the hydroxylated-THF of ACG. In addition, the hydrocarbon chain of ACGs tend to reside within the hydrophobic region between membrane monolayers composed by the acyl chains of phospholipids. The analysis of cells and supernatants obtained from cultures of polycyclic aromatic hydrocarbon degrading bacteria by chromatographic techniques and mass spectrometry allowed us to determine that the ACGs are located in the bacterial pellet, as was expected given their theoretical log P values. The localization of the ACGs, without structural modifications, in the bacterial pellet extracts, corroborates that they act only as stressors, by inducing a stress response related with an increase in AI production which in turn results in more biofilm formation.