Mini Reviews in Medicinal Chemistry - Volume 15, Issue 4, 2015

N-Aryl-5-aminopyrazole represents a key structural motif in a plethora of biologically active molecules endowed with a wide spectrum of pharmacological properties. Accordingly, this scaffold can be certainly included in the category of a privileged structure. As an example, N-aryl-5- aminopyrazole along with its 5-ureido derivatives are recurrent scaffolds in the field of inhibition of the different members of mitogen-activated protein kinases (MAPKs). Over the past recent years a large number of papers highlighting the design, synthesis and biological evaluation of different classes of N-aryl-5-aminopyrazole-containing compounds have been reported in the literature, but a review on this topic is still missing. With the aim to fill this gap, the present review article focuses on the recent developments (1995-mid2014) on the application of the N-aryl-5-aminopyrazole-based compounds in different therapeutic fields, with a particular attention to the design and structure-activity relationships (SAR) aspects of each class of compounds.

Sphingosine kinases (Sphk1 and 2) regulate the prodution of sphingosine-1-phosphate (S1P), that is key molecule in cancer development. SphK1, which is commonly overexpressed in malignant tumours, significantly contributes to the pathogenesis of various types of cancer as well as to resistance to different Tyrosine Kinase inibitors (TKIs). Even, SphK2 may promote apoptosis and inhibit cell growth but its role has not yet been fully understood in pathologic conditions. Different growth factorsinduced activation of receptor tyrosine kinases (RTKs) results in production of Sphk1 which catalyzes the phosphorylation of sphingosine. Such enzyme, in turn, is involved in many cellular processes by its five receptors. These are able to transactivate RTKs through amplification of a positive-feedback signaling loop. In conclusion, development of pharmacological inhibitors of SphK1 has been limited by the lack of completely understanding of the enzymatic activation mechanisms of SphK1.

Diabetes mellitus (DM) is a serious chronic metabolic disease which disease afflicting at present now afflicts approximately 4% of world population worldwide. Nowadays, the need for more potent and safe drugs to supply the present anti-diabetic and treated drugs has become an imperative. Astragalus membranaceus, the most common Chinese herb and key-component of many Chinese herbal anti-diabetic formulas, is rich in anti-diabetic compounds: polysaccharides (APS), saponins (ASS), and flavonoids (ASF) etc. Because of its various biological activities, especially its antidiabetic properties, that continuously arouse different studies. Recent studies focused on type 1 and type 2 treatment, respectively caused by autoimmune destruction of pancreatic beta cells and insulin resistance and deficient glucose metabolism. Its total polysaccharides, saponins and flavonoids fractions and several isolated compounds have been the most studied. This paper discusses diabetic treatment and pharmacological action of the biological ingredients in relation to diabetes mellitus and diabetic complications.

The formation of peritoneal adhesions represents one of the most common complications after abdominal surgery, and it increases the difficulty of re-operation. Thus, preventing postoperative adhesions is a major problem in the field of surgical medicine. Due to a lack of good predictive animal models and the complexity of adhesion pathogenesis, attempts to prevent or reduce peritoneal adhesions have been largely unsuccessful. As a result, the study of anti-adhesion drugs and materials has become a hot topic for experts and scholars. The processing and development of chitosan and its derivatives as new anti-adhesion materials is highly valued because chitosan is inexpensive, highly biocompatible, and not cytotoxic, making it a promising anti-adhesion material. Here, we review the sources and preparation of chitosan and the progress made toward producing different types of chitosan and its derivatives for preventing adhesion.

The endothelium represents not only a simple cellular monolayer that lines the vascular tree in humans and other vertebrates. Depending on the location, the endothelium shows significant morphological and functional heterogeneity through differentiated expression of pro- and anticoagulant factors, presence and frequency of intercellular contacts, variable contractility, cell shape, and volume. Altogether, these properties are crucial for adjustment of the endothelial function and further maintenance of the adequate homeostasis in response in local microenvironmental changes. Endothelial cells (ECs) play a critical role in coordinated regulation of blood flow. This is achieved due to the capacity of ECs to create the active anti-thrombotic surface that supports blood fluidity and transfer of blood cells and biomolecules. However, in certain vascular regions that can occur in inflamed sites or in sites with high hydrodynamic shear stress, ECs could lost their anti-thrombotic properties and switch their normal quiescent phenotype towards the prothrombotic, proadhesion, and proinflammatory state. In such an athero-prone site, the proper endothelial function is impaired that increases risk for formation of the atherosclerotic plaque. The endothelial dysfunction not only precedes atherosclerosis but greatly contributes to atherogenesis in all disease stages. Healthy lifestyle and regular intake of correct antioxidant-rich diet such as fresh fruits, vegetables, olive oil, red wine, and tea have beneficial effects on endothelial function and could therefore reduce the cardiovascular risk.