Multitarget anti-parasitic activities of isoquinoline alkaloids isolated from Hippeastrum aulicum (Amaryllidaceae)

• Published in: Phytomedicine (Stuttgart) 2024-06, Vol.128, p.155414-155414, Article 155414
• Main Authors: Bessa, Carliani Dal Piero Betzel, Feu, Amanda Eiriz, de Menezes, Renata Priscila Barros, Scotti, Marcus Tullius, Lima, Julia Maria Godoi, Lima, Marta Lopes, Tempone, Andre Gustavo, de Andrade, Jean Paulo, Bastida, Jaume, Borges, Warley de Souza
• Format: Article
• Language: English
• Subjects: Alkaloids; Alkaloids - chemistry; Alkaloids - isolation & purification; Alkaloids - pharmacology; Amaryllidaceae; Amaryllidaceae - chemistry; Animals; Antiparasitic Agents - chemistry; Antiparasitic Agents - isolation & purification; Antiparasitic Agents - pharmacology; Antiprotozoal Agents - chemistry; Antiprotozoal Agents - isolation & purification; Antiprotozoal Agents - pharmacology; Chagas disease; Hippeastrum aulicum; Humans; Isoquinolines - chemistry; Isoquinolines - isolation & purification; Isoquinolines - pharmacology; Leishmania; Leishmania infantum - drug effects; Molecular Docking Simulation; Multitarget; Plant Extracts - chemistry; Plant Extracts - pharmacology; Trypanosoma cruzi; Trypanosoma cruzi - drug effects
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2024.155414

•Amaryllidaceae species exhibit a substantial presence of alkaloids distinguished by their structures and bioactive properties.•Eleven alkaloids were previously isolated from Hippeastrum aulicum (Ker Gawl.) Herb, and five of them were now tested against trypanosoma cruzi and Leishmania infantum.•Haemanthamine and lycorine showed multitarget antiparasitic activity through in silico and in vitro analysis.•7‑methoxy-O-methyllycorenine exhibited higher activity against T. cruzi trypomastigotes. Chagas disease and leishmaniasis affect a significant portion of the Latin American population and still lack efficient treatments. In this context, natural products emerge as promising compounds for developing more effective therapies, aiming to mitigate side effects and drug resistance. Notably, species from the Amaryllidaceae family emerge as potential reservoirs of antiparasitic agents due to the presence of diverse biologically active alkaloids. To assess the anti-Trypanosoma cruzi and anti-Leishmania infantum activity of five isolated alkaloids from Hippeastrum aulicum Herb. (Amaryllidaceae) against different life stages of the parasites using in silico and in vitro assays. Furthermore, molecular docking was employed to evaluate the interaction of the most active alkaloids. Five natural isoquinoline alkaloids isolated in suitable quantities for in vitro testing underwent preliminary in silico analysis to predict their potential efficacy against Trypanosoma cruzi (amastigote and trypomastigote forms) and Leishmania infantum (amastigote and promastigote forms). The in vitro antiparasitic activity and mammalian cytotoxicity were investigated with a subsequent comparison of both analysis (in silico and in vitro) findings. Additionally, this study employed the molecular docking technique, utilizing cruzain (T. cruzi) and sterol 14α-demethylase (CYP51, L. infantum) as crucial biological targets for parasite survival, specifically focusing on compounds that exhibited promising activities against both parasites. Through computational techniques, it was identified that the alkaloids haemanthamine (1) and lycorine (8) were the most active against T. cruzi (amastigote and trypomastigote) and L. infantum (amastigote and promastigote), while also revealing unprecedented activity of alkaloid 7‑methoxy-O-methyllycorenine (6). The in vitro analysis confirmed the in silico tests, in which compound 1 presented the best activities against the promastigote and amastigote forms of L.