Current Medicinal Chemistry - Volume 21, Issue 23, 2014

The polyglutamine (polyQ) diseases including Huntington’s disease and spinocerebellar ataxias are a group of inherited neurodegenerative diseases that are caused by an abnormal expansion of the polyQ stretch in disease-causative proteins. The expanded polyQ stretches are intrinsically unstable and are prone to form insoluble aggregates and inclusion bodies. Recent studies have revealed that the expanded polyQ protei Read More

Peptides have a great potential for the treatment of neurological disorders, but the clinical translation is still facing significant hurdles. Delivery issues are among them: for example the short systemic half-life of peptides, poor passage across the blood brain barrier, slow diffusion through the extracellular space and rapid cerebrospinal fluid washout. This review will discuss new findings on the blood brain barrier and the physiol Read More

This review focuses on the therapeutic effects and mechanisms of action of NAP (davunetide), an eight amino acid snippet derived from activity-dependent neuroprotective protein (ADNP) which was discovered in the laboratory of Prof. Illana Gozes. The effects of NAP and its related peptides in models of neurodegenerative diseases and other neurological disorders will be described here in details. Possible mechanisms of NAP Read More

The treatment of central nervous system (CNS) diseases is a major challenge. The presence of the barrier intended to protect the brain from unwanted molecules also impairs the efficacy of CNS-targeted drugs. The discovery of drug targets for CNS diseases opens a door for the selective treatment of these diseases. However, the physicochemical properties of drugs, including their hydrophilic properties and their peripher Read More

Neurodegenerative diseases are characterized by selective and progressive degeneration of neuronal population in the brain, and associated behavioural, motor, psychiatric and cognitive impairments. Aggregation of pathogenic proteins, mitochondrial dysfunction, oxidative stress, transcriptional dysfunction and apoptosis play an important role in the pathogenesis of neurodegenerative disorders such as Parkinson’s Read More

Protein-protein interactions are critical for cellular functioning, and their deregulation is involved in several diseases. Targeting these protein interacting domains could be a promising approach in drug designing. One such domain, the PDZ domain is encoded by several proteins of the nervous system in particular at the postsynaptic density site of neurons where they contribute to signal transduction pathways and neur Read More

Histone deacetylase inhibitors (HDACi) have been actively explored as anti-cancer agents due to their ability to prevent deacetylation of histones, resulting in uncoiling of chromatin and stimulation of a range of genes associated in the regulation of cell survival, proliferation, differentiation and apoptosis. During the past several years, many HDACi have entered pre-clinical or clinical research as anti-cancer agents with satisfying Read More

In efforts to find agents with improved biological activity against cancer cells, recent years have seen an increased interest in the study of small molecules able to bind the deoxyribonucleic acid (DNA) when it assumes secondary structures known as G-quadruplexes (G4s) preferring them over the B form. Currently, several compounds reported in literature have already shown to be good candidates as G4s DNA stabilizers. Read More

Kinesin spindle protein (KSP) plays an essential role in centrosome separation and formation of the bipolar mitotic spindle. Its exclusive involvement in the mitotic spindle of proliferating cells presents an opportunity for developing new anticancer agents with reduced side effects relative to antimitotics that target tubulin. Small molecule KSP inhibitors have demonstrated their potential as novel antimitotic agents. Several KS Read More

Apoptosis is a highly programmed cell death strictly connected to the pathogenesis of many human diseases, including neoplastic, neurodegenerative or cardiovascular diseases. Mitochondria play a key role in the apoptotic process; their damage activates a series of events which provoke the release of cytochrome c and other pro-apoptotic factors from the mitochondrial intermembrane space, and culminat Read More

Novel sulfa Schiff bases were synthesized and characterized by a reaction between aromatic sulfonamides and aromatic aldehydes or heterocyclic ketones in equimolar ratios. Their cytotoxicity was evaluated by the resazurin assay towards human sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cells. Three of the tested compounds viz., 4-(anthracen-9-ylmethyleneamino)-N-(pyrimidin-2-yl)benzenesulfona Read More