Anti‐Trypanosomatid and Antiplasmodial Activities of Alkaloids From <i>Hippeastrum</i> Species

Diseases caused by trypanosomatid parasites like human African trypanosomiasis (HAT), Chagas disease (CD), leishmaniasis, and malaria are persistent health problems in developing countries that still demand new drug development. The species of the Amaryllidoideae subfamily (Amaryllidaceae) represent a vast source of alkaloids with a wide range of bioactive properties, including antiparasitic effects. The aim of this study was to evaluate the antiparasitic activity of the alkaloids hamayne, 7-hydroxyclivonine, 4-O-methylnangustine, and candimine against Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani, and Plasmodium falciparum parasites. The alkaloids were isolated from the leaves of Hippeastrum argentinum and Hippeastrum escoipense using several chromatographic techniques and then identified by GC-MS, UPLC-MS/MS, and NMR data. The compounds were assessed against different life cycle stages of these four parasites. Furthermore, the cytotoxic activity of the alkaloids against L6 rat skeletal myoblast cells was tested. P. falciparum was very sensible to 7-hydroxyclivonine. Candimine showed significant antiparasitic activity against all the evaluated parasites, especially T. b. rhodesiense. Candimine merits deeper research regarding its effect against trypanosomatid parasites as a lead compound for the development of alternative treatments for HAT, CD, and malaria.