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

dc.contributor.authorBetzel Bessa, Carliani Dal Piero
dc.contributor.authorEiriz Feu, Amanda
dc.contributor.authorde Menezes Barros, Renata Priscila
dc.contributor.authorTullius Scotti, Marcus
dc.contributor.authorGodoi Lima, Julia Maria
dc.contributor.authorLopes Lima, Marta
dc.contributor.authorTempone, Andre Gustavo
dc.contributor.authorde Andrade, Jean Paulo
dc.contributor.authorBastida, Jaume
dc.contributor.authorde Souza Borges, Warley
dc.date.accessioned2024-04-23T15:41:01Z
dc.date.available2024-04-23T15:41:01Z
dc.date.issued2024
dc.identifier.urihttp://repositorio.ucm.cl/handle/ucm/5346
dc.description.abstractBackground 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. Purpose 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. Methods 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. Results 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. infantum with half-maximal inhibitory concentration (IC50) 0.6 µM and 1.78 µM, respectively. Compound 8 exhibited significant activity against the amastigote form of T. cruzi (IC50 7.70 µM), and compound 6 demonstrated activity against the trypomastigote forms of T. cruzi and amastigote of L. infantum, with IC50 values of 89.55 and 86.12 µM, respectively. Molecular docking analyses indicated that alkaloids 1 and 8 exhibited superior interaction energies compared to the inhibitors. Conclusion The hitherto unreported potential of compound 6 against T. cruzi trypomastigotes and L. infantum amastigotes is now brought to the forefront. Furthermore, the acquired dataset signifies that the isolated alkaloids 1 and 8 from H. aulicum might serve as prototypes for subsequent structural refinements aimed at the exploration of novel leads against both T. cruzi and L. infantum parasites.es_CL
dc.language.isoenes_CL
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 Chile*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/*
dc.sourcePhytomedicine, 128, 155414es_CL
dc.subjectAmaryllidaceaees_CL
dc.subjectAlkaloidses_CL
dc.subjectChagas diseasees_CL
dc.subjectHippeastrum aulicumes_CL
dc.subjectLeishmaniaes_CL
dc.subjectMultitargetes_CL
dc.subjectTrypanosoma cruzies_CL
dc.titleMultitarget anti-parasitic activities of isoquinoline alkaloids isolated from Hippeastrum aulicum (Amaryllidaceae)es_CL
dc.typeArticlees_CL
dc.ucm.facultadFacultad de Medicinaes_CL
dc.ucm.indexacionScopuses_CL
dc.ucm.indexacionIsies_CL
dc.ucm.urisciencedirect.ucm.elogim.com/science/article/pii/S0944711324000795?via%3Dihubes_CL
dc.ucm.doidoi.org/10.1016/j.phymed.2024.155414es_CL


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