RESUMEN
Chronic kidney disease of unknown etiology (CKDu) has been recognized as a global non-communicable health issue. There are many proposed risk factors for CKDu and the exact reason is yet to be discovered. Understanding the inhibition or manipulation of vital renal enzymes by pesticides can play a key role in understanding the link between CKDu and pesticides. Even though it is very important to take metabolites into account when investigating the relationship between CKDu and pesticides, there is a lack of insight regarding the effects of pesticide metabolites towards CKDu. In this study, a computational approach was used to study the effects of pesticide metabolites on CKDu. Further, interactions of selected pesticides and their metabolites with renal enzymes were studied using molecular docking and molecular dynamics simulation studies. It was evident that some pesticides and metabolites have affinity to bind at the active site or at regulatory sites of considered renal enzymes. Another important discovery was the potential of some metabolites to have higher binding interactions with considered renal enzymes compared to the parent pesticides. These findings raise the question of whether pesticide metabolites may be a main risk factor towards CKDu.
Asunto(s)
Biología Computacional/métodos , Riñón/enzimología , Plaguicidas/efectos adversos , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/etiología , Sitios de Unión , Dominio Catalítico , Progresión de la Enfermedad , Humanos , Enlace de Hidrógeno , Ligandos , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Análisis de Componente Principal , Unión Proteica , Factores de Riesgo , SolventesRESUMEN
Density functional theory (DFT) was used to explore the antioxidant properties of some naturally occurring dietary vitamins, and the reaction enthalpies related to various mechanisms of primary antioxidant action, i.e., hydrogen atom transfer, single electron transfer-proton transfer, and sequential proton loss-electron transfer were discussed in detail. B3LYP, M05-2X, and M06-2X functionals were utilized in this work. For aqueous phase studies, the integral equation formalism polarized continuum model (IEF-PCM) was employed. From the outcomes, hydrogen atom transfer (HAT) was the most probable mechanism for the antioxidant action of this class of compounds. Comparison of found results with experimental data (available in literature), vitamin C possesses the lowest enthalpy values for both proton affinity (PA) and bond dissociation energy (BDE)in the aqueous phase, suggesting it as the most promising candidate as an antioxidant. Accordingly, these computational insights encourage the design of structurally novel, simple vitamins which will be more economical and beneficial in the pharmaceutical industry.
Asunto(s)
Antioxidantes/química , Vitaminas/química , Antioxidantes/farmacología , Suplementos Dietéticos , Sinergismo Farmacológico , Enlace de Hidrógeno , Modelos Moleculares , Modelos Teóricos , Conformación Molecular , Estructura Molecular , Relación Estructura-Actividad , Vitaminas/farmacologíaRESUMEN
Irradiation of the nine-membered ring enediyne precursor, which has one of its triple bonds masked as cyclopropenone, efficiently (Phi = 0.34) generates the reactive 4,5-benzocyclonona-2,6-diynol. The latter rapidly equilibrates with the corresponding 1,4-didehydronaphthalene diradical and then undergoes rate-limiting hydrogen abstraction to produce the ultimate product of the Bergman cyclization, benz[f]indanol.