Evaluación in silico de flavonoides como potenciales inhibidores del fentanilo

Abstract

The growing concern over the use of fentanyl, due to its abuse and adverse effects, underscores the urgent need to find safer therapeutic alternatives. The general objective of this research is to evaluate the interaction of secondary metabolites with the mu opioid receptor (MOR) and their use as fentanyl inhibitors through an in silico approach. The research process was divided into several key stages: initially, detailed molecular docking was performed to evaluate the initial interaction of the compounds with the receptor. Subsequently, massive docking was carried out using a broad database of natural compounds, followed by an ADMET analysis to evaluate the absorption, distribution, metabolism, excretion, and toxicity of the selected compounds. The docking results showed consistency with the receptor's crystal structure, validating the methodology used. The most promising compounds were ZINC_1297, ZINC_287, ZINC_1299, ZINC_1474, ZINC_1793, ZINC_2014, ZINC_819, ZINC_2302, ZINC_1605, ZINC_2050, ZINC_2179, and ZINC_2513, those that did not violate more than three of Lipinski's rules, ensuring their viability as effective oral drugs. Additionally, the possible relationship between hydrogen bonds and the permeability of the blood-brain barrier was explored, suggesting that these interactions may facilitate the passage of the compounds into the brain. In conclusion, this research not only advances the identification of potential natural inhibitors of fentanyl but also establishes a robust methodological framework for future explorations of natural compounds in addiction treatment and pain management, significantly contributing to mitigating the opioid crisis and developing safer and more effective therapies.