Current Medicinal Chemistry - Volume 19, Issue 31, 2012

Since their discovery by Bangham about 50 years ago, liposomes have become promising tools in drug delivery systems. This has increased the therapeutic index of many drugs, and offers improved drug targeting and controlled release. In order to further improve the specificity of liposomes for malignant tissues, targeted liposomal formulations have been developed which represent the next step of liposomal drug Read More

Cancer cachexia is a complex catabolic state in patients with a malignancy, associated with increased morbidity and mortality. This syndrome is characterized by a redistribution of the body's protein content and a subsequent muscle wasting. The aetiology of this syndrome seems multifactorial, but remains unclear. It is suggested that this catabolic state occurs in response to the alterations in immune interactions Read More

Flavonoids, secondary metabolites ubiquitously produced in the plant kingdom, are low molecular weight polyphenolic molecules. They are characterized by variable chemical structures and show a vast array of biological activities (i.e... antiviral, antiinflammatory, antitumor, antimicrobial, estrogenic, antiestrogenic, antioxidant, mutagenic and antimutagenic) targeting different pathways. Some of these comp Read More

Protein kinases (PKs) and lipid kinases (LKs) are good choices for targets of signal transduction therapy as these enzymes are involved in signaling pathways, and are often related to the pathogenesis of lymphoid malignancies. The attractiveness of PKs and LKs as drug able targets is enhanced by the fact that they are enzymes whose biological activity can be turned off by drugs that block their catalytic site. In the last few years Read More

Reactive Oxygen Species are involved in the pathological development of many important human diseases such as neurodegenerative diseases, cardiovascular processes, diabetes and many others. The most promising strategy to prevent from the oxidative damage caused by these reactive species is the use of antioxidant molecules. These compounds can act as direct antioxidants through free radical scavenging mechanis Read More

The chemistry underlying how diazabicycloheptanes are assembled is described, subdivided according to chemical structure of two types, the 3,6 diazabicyclo[3.1.1]heptane and the 2,5-diazabicyclo[2.2.1]heptane ring system. Detailed information on myriad of activities of compounds derived from the two scaffolds are reported.

In addition to the nucleoside reverse transcriptase inhibitors (NRTIs), protease inhibitors (PIs) and integrase inhibitors (INIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs) have contributed significantly in the treatment of HIV-1 infections. More than 60 structurally different classes of compounds have been identified as NNRTIs, which are specifically inhibiting HIV-1 reverse transcriptase (RT). Five NNRTIs (nevirapine, de Read More

The enzyme indoleamine 2,3-dioxygenase 1 (IDO1) finely regulates both innate and adaptive immune responses through the degradation of the essential amino acid tryptophan into kynurenine and other downstream metabolites, which suppress effector T-cell function and promote the differentiation of regulatory T cells. A novel role for IDO1 as a signaling molecule and a modifier of innate inflammatory responses is no Read More

We have previously shown that the mitochondrial potassium channel Kv1.3 (mtKv1.3) in T lymphocytes is a novel target of Bax. Mutation of Bax at lysine 128 (BaxK128E) abrogates its inhibitory effects on mtKv1.3 and prevents apoptosis. The importance of mtKv1.3 inhibition was underscored by the finding that membrane-permeant Kv1.3 inhibitors induced Bax/Bak-independent cell death and reduced the volume of an mtKv1. Read More

The excessive activation of neutrophils generates reactive oxygen species (ROS) and the secretion of primary granular enzymes, such as myeloperoxidase (MPO), which is implicated in numerous inflammatory diseases. The aim of this study was to evaluate chalcones as inhibitors of the chlorinating activity of MPO using in vitro and ex vivo assays. In addition to cytotoxic properties, the inhibition of respiratory burst, th Read More

Physalia physalis is a marine cnidarian from which high molecular weight toxins with hemolytic and neurotoxic effects have been isolated. In the present work, two novel toxins, PpV9.4 and PpV19.3 were purified from P. physalis by bioactive guideline isolation. It involved two steps of column chromatography, gel filtration and RP-HPLC. The molecular weights were 550.7 and 4720.9 Da for PpV9.4 and PpV19.3, respectively. In t Read More