Pharmacological Potential of Peruvian Eustephia Species (Amaryllidaceae): Alkaloid Diversity, Cholinesterase Inhibition, and Anti-Trypanosoma cruzi Activity

Abstract

The Amaryllidaceae family represents a prolific source of pharmacologically active compounds, boasting over 700 diverse alkaloids identified to date. However, the genus <i>Eustephia</i> (Amaryllidoideae subfamily) remains largely unexplored. This study focused on the alkaloid profiles and pharmacological potential of bulb and leaves extracts from three Peruvian <i>Eustephia</i> species (<i>E. coccinea</i>, <i>E. darwinii</i>, and <i>E. hugoei</i>). The phenolic and flavonoid levels as well as the antioxidant activity of the methanolic extracts, were determined. Twenty-six alkaloids were identified in the alkaloid-enriched extracts (AEEs). Homolycorine-type alkaloids predominated in <i>E. darwinii</i> and <i>E. hugoei</i>, whereas <i>E. coccinea</i> displayed greater chemical diversity showing assoanine as the main detected alkaloid. In addition, candimine was widely distributed across species. AEEs showed stronger enzyme inhibition of acetylcholinesterase (AChE) compared to butyrylcholinesterase (BuChE). Notably, the AEE from <i>E. coccinea</i> leaves showed the highest AChE inhibition (IC₅₀ = 1.82 μg/mL), while the AEE from bulbs exhibited the strongest BuChE inhibitory activity (IC₅₀ = 61.22 μg/mL). Regarding anti-<i>T. cruzi</i> effect, the <i>E. darwinii</i> bulbs AEE was most potent and selective against amastigote forms (IC₅₀ = 2.1 μg/mL; SI = 8.83). These findings underscore the potential of Peruvian <i>Eustephia</i> species as promising sources of pharmacologically relevant alkaloids, with possible applications in neurodegenerative disorders and Chagas disease.