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ORIGINAL RESEARCH article
Front. Chem.
Sec. Theoretical and Computational Chemistry
Volume 12 - 2024 |
doi: 10.3389/fchem.2024.1394126
IN SILICO STUDIES ON LEISHMANICIDE ACTIVITY OF LIMONOIDS AND FATTY ACIDS FROM Carapa guianensis Aubl
Provisionally accepted- 1 Federal University of Pará, Belém, Brazil
- 2 Faculty of Pharmacy, Federal University of Pará, Belém, Brazil
- 3 Federal University of Pará, Belém, Pará, Brazil
- 4 Evandro Chagas Institute, Ananindeua, Brazil
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, 7deacetoxy-7-oxogedunin, Andirobin, 6-hydroxy-angolensate methyl, 17β-hydroxyazadiradione, 1,2dihydro-3β-hydroxy-7-deacetoxy-7-oxogedunin, xyllocensin k, 11beta-Hydroxygedunin, 6α,11-11βdiacetoxygedunin, 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.
Keywords: Methyl angolensate 1, 6-hydroxy-methyl angolensate 2, Arachidic acid 3, Myristic acid 4, COX-2, hypoxia-inducibke factor 1 alpha
Received: 01 Mar 2024; Accepted: 01 Jul 2024.
Copyright: © 2024 De Barros, Farias, De Albuquerque, Marinho, Campos, Marinho and Dolabela. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Suelem D. Farias, Faculty of Pharmacy, Federal University of Pará, Belém, Brazil
Kelly C. De Albuquerque, Federal University of Pará, Belém, Pará, Brazil
Marliane B. Campos, Evandro Chagas Institute, Ananindeua, Brazil
Patrícia S. Marinho, Federal University of Pará, Belém, Brazil
Maria F. Dolabela, Faculty of Pharmacy, Federal University of Pará, Belém, Brazil
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