Diseño racional de fármacos derivados del 3-nitroxipropanol como alternativa para la inhibición de metano proveniente del microbioma metanogénico en ganado doméstico

Abstract

The study focused on mitigating methane emissions from ruminants, a greenhouse gas, through the design of new molecules. Based on an existing patent, a QSAR approach was used to design 78 molecules, prioritizing aromatic and halogen structures that had not been previously explored. Using computational methods such as AutoDock Tools, VINA, Pre-ADMET, and physicochemical property analysis, the affinity energy, toxicity, and ADME (absorption, distribution, metabolism, and excretion) characteristics of the candidate molecules were evaluated. The best candidate identified was 3-(3-fluoro-4-hydroxyphenyl)propyl nitrate, which showed an affinity energy of -6.5 kcal/mol, an improved toxicity profile (with some negative mutagenic and carcinogenic results), and favorable physicochemical properties, such as good lipophilicity and solubility (Log P and Log S). Finally, two synthesis routes were proposed for this molecule based on a trisubstituted aromatic ring, concluding the viability of the compound as a potential drug for reducing methane emissions.