RESUMO
BACKGROUND: Peru is one of the most biodiverse countries in the world, which is reflected in its wealth of knowledge about medicinal plants. However, there is a lack of information regarding intestinal absorption and the permeability of natural products. The human colon adenocarcinoma cell line (Caco-2) is an in vitro assay used to measure apparent permeability. This study aims to develop a quantitative structure-property relationship (QSPR) model using machine learning algorithms to predict the apparent permeability of the Caco-2 cell in natural products from Peru. METHODS: A dataset of 1817 compounds, including experimental log Papp values and molecular descriptors, was utilized. Six QSPR models were constructed: a multiple linear regression (MLR) model, a partial least squares regression (PLS) model, a support vector machine regression (SVM) model, a random forest (RF) model, a gradient boosting machine (GBM) model, and an SVM-RF-GBM model. RESULTS: An evaluation of the testing set revealed that the MLR and PLS models exhibited an RMSE = 0.47 and R2 = 0.63. In contrast, the SVM, RF, and GBM models showcased an RMSE = 0.39-0.40 and R2 = 0.73-0.74. Notably, the SVM-RF-GBM model demonstrated superior performance, with an RMSE = 0.38 and R2 = 0.76. The model predicted log Papp values for 502 natural products falling within the applicability domain, with 68.9% (n = 346) showing high permeability, suggesting the potential for intestinal absorption. Additionally, we categorized the natural products into six metabolic pathways and assessed their drug-likeness. CONCLUSIONS: Our results provide insights into the potential intestinal absorption of natural products in Peru, thus facilitating drug development and pharmaceutical discovery efforts.
RESUMO
Objetivos. Detectar metabolitos secundarios y caracterizar estructuras químicas de flavonoides de los extractos metanólicos de hojas de dos tipos de Ruta chalepensis L. «ruda macho¼ y «ruda hembra¼. Materiales y métodos. Se elaboraron extractos metanólicos de hojas de Ruta chalepensis L. «ruda macho¼ y «ruda hembra¼. Se llevó a cabo la prueba de solubilidad de los extractos obtenidos utilizando solventes de polaridad creciente. Posteriormente, se detectaron los metabolitos secundarios presentes en los extractos mediante la ejecución del tamizaje fitoquímico, donde se utilizaron diversos reactivos Shinoda, Dragendorff, Borntrager, entre otros. Se utilizó el método de cromatografía en capa fina, espectrofotometría UV/Vis y reactivos de desplazamiento para caracterizar las estructuras químicas de los flavonoides presentes en los extractos metanólicos de hojas de Ruta chalepensis L. «ruda macho¼ y «ruda hembra¼. Resultados. El extracto metanólico de hojas de Ruta chalepensis L. «ruda macho¼ presentó una mayor afinidad por solventes polares, mientras que en el extracto metanólico de hojas de Ruta chalepensis L. «ruda hembra¼ fue soluble en solventes medianamente polares. Se detectaron metabolitos secundarios tales como: taninos, alcaloides y flavonoides en ambos tipos. Por otro lado, se caracterizaron diez estructuras químicas tipo flavonoides a través del análisis de los espectros UV/Vis y utilizando reactivos de desplazamiento, de las cuales cinco corresponden a Ruta chalepensis L. «ruda macho¼ y las restantes a Ruta chalepensis L. «ruda hembra¼. Conclusiones. Se detectaron algunos metabolitos secundarios caracterizándose diez estructuras químicas de flavonoides en los extractos metanólicos de hojas de Ruta chalepensis L. «ruda macho¼ y «ruda hembra¼. Asimismo, la presencia de rutina en «ruda hembra¼ es la principal característica que la diferencia de «ruda macho¼.
Objective. To detect the secondary metabolites and characterize the chemical structures of the flavonoids in the methanolic extracts of leaves of the Ruta chalepensis L. "ruda macho" and "ruda hembra" types. Materials and methods. We elaborate the methanolic extracts of Ruta chalepensis L. leaves "ruda macho" and "ruda hembra". Then, the solubility test of the obtained extracts was carried out using solvents of increasing polarity. Subsequently, the secondary metabolites present in the extracts were detected by executing the phytochemical screening, various reagents were used: Shinoda, Dragendorff, Borntrager, among others. The method of thin layer chromatography, UV / Vis spectrophotometry and displacement reagents was used to characterize the chemical structures of the flavonoids in the methanolic extracts of leaves of the Ruta chalepensis L. "ruda macho" and "ruda hembra". Results. The methanolic extract of Ruta chalepensis L. "ruda macho" leaves showed a greater affinity for polar solvents, while the methanolic extract of Ruta chalepensis L. "ruda hembra" leaves was soluble in moderately polar solvents. Secondary metabolites were detected, such as: tannins, alkaloids and flavonoids in both types. On the other hand, ten flavonoidtype chemical structures were characterized through the analysis of UV / Vis spectra and using displacement reagent, of which five of them correspond to Ruta chalepensis L. "ruda macho" and the others to Ruta chalepensis L. "ruda hembra". Conclusions. Some secondary metabolites were detected and ten chemical structures of flavonoids were characterized in the methanolic extracts of Ruta chalepensis L. "ruda macho" and "ruda hembra" leaves. Likewise, the presence of rutina in "ruda hembra" is the main characteristic that differentiates it from "ruda macho".