In Silico Prediction of the Toxic Potential of Lupeol

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.