Mini Reviews in Medicinal Chemistry - Volume 12, Issue 14, 2012

Mimics of oligosaccharides capable of interfering with lectin activity are currently being pursued by a number of groups in an effort to produce tools for glycobiology and to design antagonists of medically relevant lectins. The field is reviewed in this chapter. After a brief overview of the state of the art, examples from our and others' studies on the dendritic cell receptor DC-SIGN are illustrated.

Shikimic acid, a natural compound is a key intermediate in the biosynthesis of amino acids. Consequently, this derivative is widely present in many plants and has interesting biological properties. But besides the pharmacological relevance of shikimic acid itself, it is also an intermediate in the synthesis of many drugs, being the most relevant the antiviral agent oseltamivir (TamifluTM). Here we present a short overview on recent natural, biotechnological and synthetical sources of shikimic acid, togheter with pharmacological applications of this compound and a selection of derivatives, including oseltamivir (TamifluTM).

Fucosyltransferases (FucTs) are enzymes that transfer L-fucose from GDP-fucose to a glycoside or a peptide. They have important roles in a variety of diseases including cancer and autoimmune disorders, viral and bacterial infections and inflammatory processes, and thus they represent important drug targets for the development of agents for the treatment of such disorders. This review highlights recent developments regarding carbohydrate mimics as inhibitors of FucTs. The most recent and relevant synthetic strategies are described.

This comprehensive review deals with the synthesis of 1-azafagomine, analogs, and derivatives having the Diels-Alder cycloaddition as the key step. Most of the compounds referred are racemic or have been resolved by lipase transesterification. There are two asymmetric cycloadditions leading to 1-azafagomine or to an analog. In one case both enantiomers of 1-azafagomine were prepared together with a pair of derivatives. The study comprises glycosidase inhibition studies of the target compounds to a set of glycosidic enzymes, and evidenced molecular features that enhance or diminish their activity as glycosidase inhibitors.

The revision of the structures and properties of Calystegines shows that they can be regarded as carbohydrate mimics, with related biological activities and peculiar characteristics. Not only they can be isolated from food plants, but they can be obtained from a variety of monosaccharide derivatives and of non-carbohydrate products. Although several synthetic calystegine analogs have been reported as glycosidase inhibitors, new, more potent and effective inhibitors are required.

This review describes some spiro- and pseudospironucleoside derivatives as well as their biological and pharmacological applications.

In addition to being valuable source of energy, carbohydrates, one of the main dietary components, are integral parts of the cell. As extra- & intracellular molecules they act as cell surface receptor and also as signaling molecules playing predominant role in molecular recognition and many other cellular processes. The clear understanding of their role in the various important biological events has led to the demand for easy access of diverse glycoconjugates for their complete chemical and biological investigations. Several carbohydrate-based molecules both of synthetic and natural origin are known for their wide range of pharmacological activities and even many of them are clinically used to treat different ailments. Due to their structural diversity in terms of functional groups, ring size and linkages they are valuable scaffolds in drug discovery processes. Because of the hydrophilic nature of monosaccharides they offer good water solubility, optimum pharmacokinetics and decreased toxicity. These naturally occurring molecules have therefore been extensively used to access diverse library of compounds with great chemotherapeutic importance. This review highlights an overview of development of carbohydrate-based molecules from others and our lab which have shown promising biological activity against front line diseases.

The mycalamide class of potent antiviral and antitumor natural compounds originally isolated from marine sponges in 1988 is a new interdisciplinary approach to molecular recognition. We review new synthetic approaches to this new family of natural products with remarkable biological activity. Some biological evaluation data are compiled and compared to other structurally similar molecular targets.

With the development of glycomics, more and more carbohydrate mimetics were used to investigate the interactions between carbohydrate-proteins, especially in physiological and pathological processes, molecular recognition, signal transduction, cell communication, cell differentiation and developmental events. Recently, because of the drugresistance of microorganisms and the development of antibiotics, the interactions between carbohydrate mimetics and RNAs are becoming hot issue. Aminoglycosides, one family of important antibiotics, can bind with 30S subunits of rRNA to prevent the normal translations of proteins, inhibit the proteins involving in the drug-resistance. In this review, the latest advances in development and applications of aminoglycosides are summarized and the detailed descriptions on the SAR study (Structure-activity relationship) of aminoglycoside derivatives are discussed.

Relationship between biological responses and binding affinities at I1/I2/I3 imidazoline receptors of compounds with imidazoline, pyrroline or oxazoline moieties was studied by 2D-QSAR, 3D-QSAR and quantitative pharmacophore development approaches. Since the I1 imidazoline receptor is involved in central inhibition of sympathicus that produce hypotensive effect, the I2 receptor is allosteric modulator of monoamine oxidase B (MAO-B) and the I3 receptor regulates insulin secretion from pancreatic β-cells, design and synthesis of selective I1/I2/I3 imidazoline ligands are very important for the development of new effective therapeutic agents. New agonists and antagonists with high selectivity for I1/I2/I3 imidazoline receptor classes have been recently synthesized and examined. The present review will highlight the main chemical diversity and pharmacophore features of selective I1/I2/I3 imidazoline receptor ligands.

Parkinson's disease (PD) is a neurodegenerative condition characterized by progressive and profound loss of dopaminergic neurons in the substantia nigra pars compacta leading to the formation of eosinophillic, intracytoplamic, proteinacious inclusions termed as lewy bodies. L-dopa remains as a gold standard for the treatment of PD, and is often combined with carbidopa to reduce the dose-limiting side effects. Long-term levodopa treatment is associated with the development of motor fluctuations and peak dose dyskinesias. Dopamine Replacement Therapy (DRT) with dopamine agonists (DAs) (ropinirole and pramipexole) is used to manage complications of L-dopa treatment, however, has been associated with numerous pharmacovigilence reports. The present review attempts to narrate the multiple receptor interaction of DAs followed by the assessment of their side effects during the treatment of PD and possible remedial strategy for selective targeting of dopamine receptors to overcome these affects in therapy of Parkinson's disease.