Mini Reviews in Medicinal Chemistry - Volume 14, Issue 6, 2014

Cellular responses to the environment are mediated by intracellular signalling pathways monitoring several essential cellular processes, such as proliferation, migration, differentiation and survival. Cellular dysfunction is caused by dysregulation of intracelleular signalling pathways and may ultimately result in pathophysiological conditions. The non- transmembrane protein tyrosine phosphatase SHP-2 has been shown to be important for the control of cellular behaviour. It influences the activity of several growth factor and cytokine dependent signalling pathways by association with growth factor receptors, cell surface adhesion molecules and adaptor molecules such as Gab-1, Grb2 and IRS-1. Upon FGF-2, EGF and insulin stimulation SHP-2 regulates MAPK pathway activation. In addition, SHP-2 is involved in the regulation of cell survival by influencing the PI3-K/Akt pathway upon EGF, IGF and PDGF stimulation. Due to these properties, SHP-2 function has recently gained more interest in vascular processes, such as in the differentiation of cardiac progenitor cells and angiogenic events. Indeed, SHP-2 was shown to positively regulate endothelial cell motility and angiogenesis in vitro and in vivo as well as controlling intracellular pH of endothelial and vascular smooth muscle cells. On the other hand, SHP-2 was also demonstrated to be responsible for down regulation of VEGF receptor 2 activation upon dopamin and collagen stimulation. Finally, mutations in the Ptpn11 gene (encoding SHP-2) underlie the developmental disorders Noonan syndrome and Leopard syndrome characterized by congenital heart disease and hematologic abnormalities. Different mutations in this gene also result in myeloid and lymphoid malignancies. This article summarizes the role of SHP-2 in signalling pathways relevant for vascular biology and associated disorders.

Most drugs are carried from the site of absorption to their intended site of action (target site) by the bloodstream, either dissolved in the serum or bound to plasma proteins. Binding to plasma proteins influences (i.e. limits or favours), drug distribution through the body. Usually it is the unbound drug concentration that determines its pharmacological and toxicological properties. Our ability to design suitable drug candidates depends on our ability to understand the molecular characteristics of drug-protein binding and ideally be able to predict the extent of binding in vivo. Here we review the different approaches that have been used to model and predict the binding of drugs and drug like molecules to plasma proteins in the body.

Many of nowadays diseases are due to the oxidative stress resulting from imbalance between formation and neutralization of free radicals. Intake of dietary antioxidants is therefore crucial to maintain good health. As the safety of synthetic antioxidants has raised several questions the search for natural efficient antioxidants from chemicals produced by plants has gained increased popularity in recent years. Quercetin is an abundant dietary flavonoid with well-known radical scavenging properties being often used as a reference compound in many antioxidant tests. Its reaction with 1,1- diphenyl-2-picrylhydrazyl (artificial DPPH radical) is rapid and stoichiometric; however the published inhibitory constants vary in a very wide range, from 95 nM to 226 μM. The analysis indicates the dependence of antiradical capacity of quercetin on the composition of solvent systems where the reactions are performed and also on the surrounding temperature showing somewhat higher scavenging ability at body temperature compared to room conditions. At the same time, this activity is generally independent on the initial DPPH concentration. These data highlight the importance to consider the reaction environment and conditions when predicting the redox behavior of quercetin in a certain cellular context. Moreover, due to the changes in cellular environment accompanying with different pathogeneses the redox action of polyphenols can essentially vary leading even to the situations where the well-known antioxidant quercetin may reveal prooxidant properties.

Coronary artery stents used for the treatment of patients with coronary artery disease develop the practice of interventional cardiology after they were first introduced in the mid-1980s. Since then, with dozens of companies involved in the development of new and innovative anti-restenotic drugs, polymeric coatings and stent platforms has made significant progress in this area. Today, the challenge is the conception of the “ideal” coronary stent designed to respond to the patient health difficulty. In this context, the literature in the field is quite dynamic and successful. The aim of this article is to provide a systematic review on the interdisciplinary field literature of the evolution of these medical devices by describing the current status, importance and different types of stents used in clinical practice. After the presentation of cardiovascular problems associated to stenting therapy, the authors describe the bare metal stents, the generations of drug eluting stents and the future in progress directions regarding: the stents based on biodegradable/bioresorbable polymers, polymer-free metal platforms, fully biodegradable scaffolds, as well as drug delivery mediated by stent-targeted magnetic nanoparticles.

The sea urchin is an ancient, common, seafloor-dwelling marine invertebrate that belongs to the phylum Echinodermata. There are multiple species of sea urchin with resources that are widely distributed in China, where they were used in ancient times as Traditional Chinese Medicine for treating a variety of diseases. At present, it is known that the shell, spine and gonad of the sea urchin have many medicinal values determined through modern research. In this paper, we summarized the major chemical constituents and medicinal value of the sea urchin.

Caffeine is a secondary metabolite of tea and coffee plants. It is the active psychostimulant ingredient of widely consumed beverages, chocolate and some drugs as well. The major pathways for caffeine including interaction with adenosine receptors have been identified but caffeine has several minor pathways as well that remain poorly understood including the cholinergic system. Given the role of caffeine in the cholinergic system, some molecular targets have been tracked and a mechanism of its action has been proposed in research studies. However, the biological effect of caffeine on the cholinergic system is not completely understood. The present review focuses on the role of caffeine in the cholinergic system.