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

Autor: Bessa CDPB; Programa de Pós-Graduação em Química, Departamento de Química, Universidade Federal do Espírito Santo, Vitória-ES 29075-910, Brazil., Feu AE; Programa de Pós-Graduação em Química, Departamento de Química, Universidade Federal do Espírito Santo, Vitória-ES 29075-910, Brazil., de Menezes RPB; Programa de Pós-graduação em Produtos Naturais e Sintéticos Bioativos (PgPNSB), Universidade Federal da Paraíba, Campus I, Cidade Universitária, João Pessoa 58051-900, Brazil., Scotti MT; Programa de Pós-graduação em Produtos Naturais e Sintéticos Bioativos (PgPNSB), Universidade Federal da Paraíba, Campus I, Cidade Universitária, João Pessoa 58051-900, Brazil., Lima JMG; Laboratory of Pathophysiology, Butantan Institute, São Paulo, SP 05503900, Brazil., Lima ML; School of Life Sciences, University of Dundee, Scotland DD1 4HN, United Kingdom., Tempone AG; Laboratory of Pathophysiology, Butantan Institute, São Paulo, SP 05503900, Brazil., de Andrade JP; Departamento de Medicina Traslacional, Facultad de Medicina, Escuela de Química y Farmacia, Universidad Católica del Maule, Talca 3480112, Chile., Bastida J; Departament de Biologia, Sanitat i Medi Ambient, Facultat de Farmàcia i Ciències de l´Alimentació, Universitat de Barcelona, Barcelona 08028, Spain., Borges WS; Programa de Pós-Graduação em Química, Departamento de Química, Universidade Federal do Espírito Santo, Vitória-ES 29075-910, Brazil. Electronic address: warley.borges@ufes.com.
Jazyk: angličtina
Zdroj: Phytomedicine : international journal of phytotherapy and phytopharmacology [Phytomedicine] 2024 Jun; Vol. 128, pp. 155414. Date of Electronic Publication: 2024 Feb 05.
DOI: 10.1016/j.phymed.2024.155414
Abstrakt: Background: 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 (IC 50 ) 0.6 µM and 1.78 µM, respectively. Compound 8 exhibited significant activity against the amastigote form of T. cruzi (IC 50 7.70 µM), and compound 6 demonstrated activity against the trypomastigote forms of T. cruzi and amastigote of L. infantum, with IC 50 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.
Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest.
(Copyright © 2024 Elsevier GmbH. All rights reserved.)
Databáze: MEDLINE
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