In silico studies on leishmanicide activity of limonoids and fatty acids from Carapa guianensis Aubl.

Autor: de Barros RC; Pharmaceutical Sciences Postgraduate Program, Federal University of Pará, Belém, PA, Brazil., Araujo da Costa R; Federal Institute of Education Sciences of the State of Pará, Abaetetuba, PA, Brazil., Farias SDP; Faculty of Pharmacy, Federal University of Pará, Belém, PA, Brazil., de Albuquerque KCO; Biotechnology and Biodiversity Postgraduate Program (BIONORTE), Federal University of Pará, Belém, PA, Brazil., Marinho AMR; Post-Graduation in Chemistry, Federal University of Pará, Belém, PA, Brazil., Campos MB; Leishmaniasis Laboratory, Evandro Chagas Institute, Ananindeua, PA, Brazil., Marinho PSB; Post-Graduation in Chemistry, Federal University of Pará, Belém, PA, Brazil., Dolabela MF; Pharmaceutical Sciences Postgraduate Program, Federal University of Pará, Belém, PA, Brazil.; Faculty of Pharmacy, Federal University of Pará, Belém, PA, Brazil.; Biotechnology and Biodiversity Postgraduate Program (BIONORTE), Federal University of Pará, Belém, PA, Brazil.
Jazyk: angličtina
Zdroj: Frontiers in chemistry [Front Chem] 2024 Jul 30; Vol. 12, pp. 1394126. Date of Electronic Publication: 2024 Jul 30 (Print Publication: 2024).
DOI: 10.3389/fchem.2024.1394126
Abstrakt: The oil of Carapa guianensis showed leishmanicidal activity, with its activity being related to limonoids, but fatty acids are the major constituents of this oil. The present study evaluated the physicochemical, pharmacokinetic, and toxicity profiles of limonoids and fatty acids already identified in the species. Based on these results, 2 limonoids (methyl angosinlate, 6-OH-methyl angosinlate) and 2 fatty acids (arachidic acid; myristic acid) were selected for the prediction of possible targets and molecular docking. Included in this study were: Gedunin, 6α-acetoxygedunin, Methyl angosenlato, 7-deacetoxy-7-oxogedunin, Andirobin, 6-hydroxy-angolensate methyl, 17β-hydroxyazadiradione, 1,2-dihydro-3β-hydroxy-7-deacetoxy-7-oxogedunin, xyllocensin k, 11beta-Hydroxygedunin, 6α,11-11β-diacetoxygedunin, Oleic Acid, Palmitic Acid, Stearic Acid, Arachidic Acid, Myristic Acid, Palmitoleic Acid, Linoleic Acid, Linolenic Acid, and Beenic Acid. Regarding physicochemical aspects, fatty acids violated LogP, and only limonoid 11 violated Lipinski's rule. A common pharmacokinetic aspect was that all molecules were well absorbed in the intestine and inhibited CYP. All compounds showed toxicity in some model, with fatty acids being mutagenic and carcinogenic, and limonoids not being mutagenic and carcinogenic at least for rats. In in vivo models, fatty acids were less toxic. Molecular dockings were performed on COX-2 steroids (15 and 16) and hypoxia-inducible factor 1 alpha for limonoids (3,6), with this target being essential for the intracellular development of leishmania. Limonoids 3 and 6 appear to be promising as leishmanicidal agents, and fatty acids are promising as wound healers.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2024 de Barros, Araujo da Costa, Farias, de Albuquerque, Marinho, Campos, Marinho and Dolabela.)
Databáze: MEDLINE
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