Journal article
In Silico Prediction of the Toxic Potential of Lupeol.
- Ruiz-Rodríguez MA Department of Chemical and Biochemical Engineering, Tecnológico Nacional de México-Instituto Tecnológico de Durango , Boulevard Felipe Pescador 1830 Ote., 34080 Durango, México.
- Vedani A Department of Pharmaceutical Sciences, University of Basel , Klingelbergstrasse 50, 4056 Basel, Switzerland.
- Flores-Mireles AL Department of Molecular Microbiology and Center for Women's Infectious Disease Research, Washington University School of Medicine , Saint Louis, Missouri 63110-1093, United States.
- Cháirez-Ramírez MH Department of Chemical and Biochemical Engineering, Tecnológico Nacional de México-Instituto Tecnológico de Durango , Boulevard Felipe Pescador 1830 Ote., 34080 Durango, México.
- Gallegos-Infante JA Department of Chemical and Biochemical Engineering, Tecnológico Nacional de México-Instituto Tecnológico de Durango , Boulevard Felipe Pescador 1830 Ote., 34080 Durango, México.
- González-Laredo RF Department of Chemical and Biochemical Engineering, Tecnológico Nacional de México-Instituto Tecnológico de Durango , Boulevard Felipe Pescador 1830 Ote., 34080 Durango, México.
- 2017-06-28
Published in:
- Chemical research in toxicology. - 2017
Animals
Caco-2 Cells
Cell Membrane Permeability
Cell Survival
Dogs
Humans
Hydrogen Bonding
Madin Darby Canine Kidney Cells
Mangifera
Mice
Molecular Dynamics Simulation
Pentacyclic Triterpenes
Protein Binding
Protein Structure, Tertiary
Proteins
Quantitative Structure-Activity Relationship
Rats
Receptors, Androgen
Receptors, Estrogen
Software
Thermodynamics
English
Lupeol is a natural triterpenoid found in many plant species such as mango. This compound is the principal active component of many traditional herbal medicines. In the past decade, a considerable number of publications dealt with lupeol and its analogues due to the interest in their pharmacological activities against cancer, inflammation, arthritis, diabetes, and heart disease. To identify further potential applications of lupeol and its analogues, it is necessary to investigate their mechanisms of action, particularly their interaction with off-target proteins that may trigger adverse effects or toxicity. In this study, we simulated and quantified the interaction of lupeol and 11 of its analogues toward a series of 16 proteins known or suspected to trigger adverse effects employing the VirtualToxLab. This software provides a thermodynamic estimate of the binding affinity, and the results were challenged by molecular-dynamics simulations, which allow probing the kinetic stability of the underlying protein-ligand complexes. Our results indicate that there is a moderate toxic potential for lupeol and some of its analogues, by targeting and binding to nuclear receptors involved in fertility, which could trigger undesired adverse effects.
- Language
-
- English
- Open access status
- closed
- Identifiers
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- DOI 10.1021/acs.chemrestox.7b00070
- PMID 28654752
- Persistent URL
- https://sonar.ch/global/documents/63989
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