Cardiovascular disease has been a major threat to human’s health and lives for many years. It is of great importance to explore the mechanisms and develop strategies to prevent the pathogenesis. Generally, cardiovascular disease is associated with endothelial dysfunction, which is closely related to the nitric oxide (NO)mediated vasodilatation. The release of NO is regulated by NOS3 gene in mammals’ vascular system. A great deal of evidences have shown that the polymorphism and epigenetic of NOS3 gene play vital roles in the pathological process of cardiovascular disease. To gain insights into the role of NOS3 in the cardiovascular diseases, we reviewed the molecular mechanisms underlying the development of cardiovascular diseases in this paper, including the uncoupling of NOS3 protein, epigenetic and polymorphism of NOS3 gene. The review can also offer possible strategies to prevent and treat cardiovascular diseases.
The β-secretase is one of prospective targets against Alzheimer's disease (AD). A three-dimensional quantitative structure-activity relationship (3D-QSAR) model of Hydroethylamines (HEAs) as β-secretase inhibitors was established using Topomer CoMFA. The multiple correlation coefficient of fitting, cross validation and external validation were r2=0.928, qloo2=0.605 and rpred2=0.626, respectively. The 3D-QSAR model was used to search R groups from ZINC database as the source of structural fragments. As a result, a series of R groups with relatively high activity contribution was obtained to design a total of 15 new compounds, with higher activity than that of the template molecule. The molecular docking was employed to study the interaction mode between the new compounds as ligands and β-secretase as receptors, displaying that hydrogen bond and hydrophobicity played important roles in the binding affinity between the new compounds and β-secretase. The results showed that Topomer CoMFA and Topomer Search could be effectively used to screen and design new molecules of HEAs as β-secretase inhibitors, and the designed compounds could provide new candidates for drug design targeting AD.