Scholarly

Molecular Dynamic Simulation and Receptor-based Pharmacophore Modeling on Human Renin for Discovery of Novel Inhibitors

Year: 2013 Volume: 7 Issue: 1 74 - 79 Pages

Abstract: Hypertension is characterized with stress on the heart and blood vessels thus increasing the risk of heart attack and renal diseases. The Renin angiotensin system (RAS) plays a major role in blood pressure control. Renin is the enzyme that controls the RAS at the rate-limiting step. Our aim is to develop new drug-like leads which can inhibit renin and thereby emerge as therapeutics for hypertension. To achieve this, molecular dynamics (MD) simulation and receptor-based pharmacophore modeling were implemented, and three rennin-inhibitor complex structures were selected based on IC50 value and scaffolds of inhibitors. Three pharmacophore models were generated considering conformations induced by inhibitor. The compounds mapped to these models were selected and subjected to drug-like screening. The identified hits were docked into the active site of renin. Finally, hit1 satisfying the binding mode and interaction energy was selected as possible lead candidate to be used in novel renin inhibitors.

Discovery of Human HMG-Coa Reductase Inhibitors Using Structure-Based Pharmacophore Modeling Combined with Molecular Dynamics Simulation Methodologies

Year: 2013 Volume: 7 Issue: 1 59 - 64 Pages

Abstract: 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) catalyzes the conversion of HMG-CoA to mevalonate using NADPH and the enzyme is involved in rate-controlling step of mevalonate. Inhibition of HMGR is considered as effective way to lower cholesterol levels so it is drug target to treat hypercholesterolemia, major risk factor of cardiovascular disease. To discover novel HMGR inhibitor, we performed structure-based pharmacophore modeling combined with molecular dynamics (MD) simulation. Four HMGR inhibitors were used for MD simulation and representative structure of each simulation were selected by clustering analysis. Four structure-based pharmacophore models were generated using the representative structure. The generated models were validated used in virtual screening to find novel scaffolds for inhibiting HMGR. The screened compounds were filtered by applying drug-like properties and used in molecular docking. Finally, four hit compounds were obtained and these complexes were refined using energy minimization. These compounds might be potential leads to design novel HMGR inhibitor.

Polyurethane Nanofibers Obtained By Electrospinning Process

Year: 2013 Volume: 7 Issue: 3 190 - 193 Pages

Abstract: Electrospinning is a broadly used technology to obtain polymeric nanofibers ranging from several micrometers down to several hundred nanometers for a wide range of applications. It offers unique capabilities to produce nanofibers with controllable porous structure. With smaller pores and higher surface area than regular fibers, electrospun fibers have been successfully applied in various fields, such as, nanocatalysis, tissue engineering scaffolds, protective clothing, filtration, biomedical, pharmaceutical, optical electronics, healthcare, biotechnology, defense and security, and environmental engineering. In this study, polyurethane nanofibers were obtained under different electrospinning parameters. Fiber morphology and diameter distribution were investigated in order to understand them as a function of process parameters.

Fabrication of Tissue Engineering Scaffolds Using Rapid Prototyping Techniques

Year: 2011 Volume: 5 Issue: 11 2188 - 2196 Pages

Abstract: Rapid prototyping (RP) techniques are a group of advanced manufacturing processes that can produce custom made objects directly from computer data such as Computer Aided Design (CAD), Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) data. Using RP fabrication techniques, constructs with controllable and complex internal architecture with appropriate mechanical properties can be achieved. One of the attractive and promising utilization of RP techniques is related to tissue engineering (TE) scaffold fabrication. Tissue engineering scaffold is a 3D construction that acts as a template for tissue regeneration. Although several conventional techniques such as solvent casting and gas forming are utilized in scaffold fabrication; these processes show poor interconnectivity and uncontrollable porosity of the produced scaffolds. So, RP techniques become the best alternative fabrication methods of TE scaffolds. This paper reviews the current state of the art in the area of tissue engineering scaffolds fabrication using advanced RP processes, as well as the current limitations and future trends in scaffold fabrication RP techniques.

Osteogenesis by Dextran Coating on and among Fibers of a Polyvinyl Formal Sponge

Year: 2009 Volume: 3 Issue: 6 58 - 62 Pages

Abstract: A scaffold is necessary for tooth regeneration because of its three-dimensional geometry. For restoration of defect, it is necessary for the scaffold to be prepared in the shape of the defect. Sponges made from polyvinyl alcohol with formalin cross-linking (PVF sponge) have been used for scaffolds for bone formation in vivo. To induce osteogenesis within the sponge, methods of growing rat bone marrow cells (rBMCs) among the fiber structures in the sponge might be considered. Storage of rBMCs among the fibers in the sponge coated with dextran (10 kDa) was tried. After seeding of rBMCs to PVF sponge immersed in dextran solution at 2 g/dl concentration, osteogenesis was recognized in subcutaneously implanted PVF sponge as a scaffold in vivo. The level of osteocalcin was 25.28±5.71 ng/scaffold and that of Ca was 129.20±19.69 µg/scaffold. These values were significantly higher than those in sponges without dextran coating (p

Physical and Chemical Investigation of Polycaprolactone, Nanohydroxyapatite and Poly (Vinyl Alcohol) Nanocomposite Scaffolds

Year: 2012 Volume: 6 Issue: 2 143 - 146 Pages

Abstract: Aligned and random nanofibrous scaffolds of PVA/PCL/nHA were fabricated by electrospinning method. The composite nanofibrous scaffolds were subjected to detailed analysis. Morphological investigations revealed that the prepared nanofibers have uniform morphology and the average fiber diameters of aligned and random scaffolds were 135.5 and 290 nm, respectively. The obtained scaffolds have a porous structure with porosity of 88 and 76% for random and aligned nanofibers, respectively. Furthermore, FTIR analysis demonstrated that there were strong intramolecular interactions between the molecules of PVA/PCL/nHA. On the other hand, mechanical characterizations show that aligning the nanofibers, could significantly improve the rigidity of the resultant biocomposite nanofibrous scaffolds.

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