Current Medicinal Chemistry - Volume 13, Issue 6, 2006

The cancer stem cell hypothesis suggests that neoplastic clones are maintained exclusively by a rare fraction of cells with stem cell proprieties. Stem cells are defined as cells which are able to both extensively self-renew and differentiate into progenitors. Furthermore, stem cells are also attractive candidates as origin of cancers, as in their long lifespan mutations and epigenetic changes they can increase allowing for incr Read More

Nitric oxide (NO) is an endogenous compound, which plays a fundamental role in the modulation of the function of the cardiovascular system, where it induces vasorelaxing and antiplatelet responses, mainly through the stimulation of guanylate cyclase and the increase of cGMP. Many drugs of common, timehonoured clinical use (for example, glycerol trinitrate and all the vasodilator nitrites and nitrates) act via the rele Read More

The endothelin system, consisting of three peptides, two peptidases and two G-protein coupled receptors, is widely expressed in the brain cell types and brain-derived tumor cell lines. The stimulation of endothelin receptors elicits a variety of short- and long-term changes at cellular level but the effects of the pharmacological modulation of the endothelin system in brain physiology and pathophysiology are, at the present time, po Read More

A computer-aided approach has been developed in order to understand the molecular pharmacology of human A3R, and specifically, to lead to the discovery and structural refinement of new, potent and selective human A3R antagonists. This review focuses on our combined target-based and ligand-based drug design strategy, recently applied to provide more accurate information about the recognition mode on human A3R of Read More

Ryanodine receptor (RyR) is a tetrameric, high molecular weight protein that functions as a calcium release channel. It plays a key role in phenomena such as signal transduction, excitation-contraction and excitation-secretion coupling. Hyperthermia maligna, central core disease and myocardial infarction have been related with RyR dysfunction. RyR is present as three isoforms in vertebrates: RyR 1 mainly localized in Read More

Non-steroidal anti-inflammatory drugs (NSAIDs) are of huge therapeutic benefit in the treatment of rheumatoid arthritis and various types of inflammatory conditions. The target for these drugs is cyclooxygenase (COX), a rate-limiting enzyme involved in the conversion of arachidonic acid into inflammatory prostaglandins. COX-2 selective inhibitors are believed to have the same anti-inflammatory, anti-pyretic and analgesic Read More

Antimicrobial peptides, which constitute an important component of innate immunity in animal and plant kingdom, are ubiquitously distributed in nature. However, they differ widely in their sizes, sequences and structures. On the basis of their structure they have been broadly classified into three classes: a) linear peptides with propensity for amphiphilic a-helical structure, b) peptides with β or αβ structure stabilized by differe Read More

Natural products from symbiotic or commensal associations between marine invertebrate and microbial organisms show exceptional promise as pharmaceuticals in many therapeutic areas. An economic and sustainable global market supply due to difficulty of synthesis is cited as the main obstacle for exploitation of these otherwise exciting marine bioactive compounds [1]. Different strategies have been evoked to overcom Read More

Macrocyclic polyamines comprise a special group of heterocycles that bind different guests. Over the past decade, medical interest has focused on macrocyclic polyamines owning to their chemical and biological properties. The discovery and development of the bicyclam AMD3100 highlighted the clinical potential of such compounds in AIDS, cancer and stem-cell mobilization. Many macrocyclic polyamines and their transition m Read More