Antiprotozoal Activity Against Entamoeba hystolitica and Giardia lamblia of Cyclopeptides Isolated from Annona diversifolia Saff

Diseases caused by intestinal parasites such as protozoa represent a worldwide problem mainly for developing countries. From morbidity in different groups of people to cases of mortality in children and/or immunocompromised patients. In addition to the above, there is growing resistance to the drugs used in the treatment of these diseases, as well as undesirable side effects in patients. Therefore, there is an interest in the search for new alternatives for the base and/or development of new drugs with antiparasitic activities without harmful effects. In this sense, natural products offer to be a diverse source of compounds with biological activities. In this work, we describe the isolation and elucidation by 1D and 2D NMR spectroscopy of three cyclopeptides obtained from seeds of <i>A. diversifolia</i> Saff.: cherimolacyclopeptide D (<b>1</b>), squamin D (<b>2</b>), and squamin C (<b>3</b>). The fractions enriched in cyclopeptides, as well as a pure compound (<b>1</b>), showed antiprotozoal activity against <i>E. hystolitica</i> Schaudinn and <i>Giardia lamblia</i> Kunstler in vitro assays, with values of IC₅₀ = 3.49 and 5.39 μg mL^-1, respectively. The molecular docking study revealed that <b>1</b> has a strong interaction with targets used, including aldose reductase and PFOR enzymes. The antiprotozoal activity of cherimolacyclopeptide D is reported for the first time in this study.