Docking of novel reversible monoamine oxidase-B inhibitors: efficient prediction of ligand binding sites and estimation of inhibitors thermodynamic properties

Monoamine oxidase (MAO, EC 1.4.3.4) is a flavoenzyme bound to the mitochondrial outer membranes of the cells, which is responsible for the oxidative deamination of neurotransmitter and dietary amines. It has two distinct isozymic forms, designated MAO-A and MAO-B, each displaying different substrate and inhibitor specificities. They are the well-known target for antidepressant, Parkinson?s disease and neuroprotective drugs. Elucidation of the x-ray crystallographic structure of MAO-B has opened the way for molecular modeling studies. In this research 12 reversible and MAO-B selective inhibitors have been docked computationally to the active site of the MAO-B enzyme. AutoDock 3.0.5 was employed to perform the automated molecular docking. The result of docking studies generated thermodynamic properties, such as free energy of bindings (?Gb) and inhibition constants (K i) for the inhibitors. Moreover, 3D pictures of inhibitor-enzyme complexes afforded valuable data regarding the binding orientation of each inhibitor in the active site of MAO-B

Age-associated changes in nitric oxide metabolites nitrite and nitrate

WOS: 000089506400004PubMed ID: 11043501Aging is an important determinant of vascular disease. Endothelial dysfunction accompanying vascular disease may be related to cardiovascular risk factors such as aging, hypertension, and atherosclerosis. Experimental models suggest that endothelium-derived nitric oxide is reduced with aging, and this reduction is implicated in atherogenesis. The aim of this study was to determine whether increased age resulted in altered serum nitrite and nitrate levels, end-products of nitric oxide, in healthy subjects. Sixty-nine healthy individuals were divided into five different age groups: group I (6-15 years), group II (16-30 years), group III (31-45 years), group IV (46-60 years), and group V (>61 years). In these subjects, serum nitrite was measured by the Griess reaction and nitrate by the nitrate reductase method. Statistical analysis showed that serum nitrite levels were not significantly different in any of the groups, while serum nitrate concentrations exhibited significant differences (P<0.001). These findings suggest that nitric oxide synthesis and/or secretion is reduced with age and consequently endothelium-dependent vasodilation is impaired

Tailored surface structure of LiFePO4/C nanofibers by phosphidation and their electrochemical superiority for lithium rechargeable batteries

We offer a brand new strategy for enhancing Li ion transport at the surface of LiFePO4/C nanofibers through noble Li ion conducting pathways built along reduced carbon webs by phosphorus. Pristine LiFePO4/C nanofibers composed of 1-dimensional (1D) LiFePO4 nanofibers with thick carbon coating layers on the surfaces of the nanofibers were prepared by the electrospinning technique. These dense and thick carbon layers prevented not only electrolyte penetration into the inner LiFePO4 nanofibers but also facile Li ion transport at the electrode/electrolyte interface. In contrast, the existing strong interactions between the carbon and oxygen atoms on the surface of the pristine LiFePO4/C nanofibers were weakened or partly broken by the adhesion of phosphorus, thereby improving Li ion migration through the thick carbon layers on the surfaces of the LiFePO4 nanofibers. As a result, the phosphidated LiFePO4/C nanofibers have a higher initial discharge capacity and a greatly improved rate capability when compared with pristine LiFePO4/C nanofibers. Our findings of high Li ion transport induced by phosphidation can be widely applied to other carbon-coated electrode materials.close2