Current Medicinal Chemistry - Volume 16, Issue 35, 2009

The immune system balances effector responses with tolerance, to protect the host from pathogens while minimizing local damage to tissue. An altered control of immune homeostasis can lead to loss of tolerance to self antigens in autoimmunity, or promote unwanted tolerance to tumor growth. This review focuses on the dual activity of CD4+ regulatory T cells (Tregs) in autoimmunity and cancer. Tregs play a key role in t Read More

Many drugs that are currently used for the treatment of cancer have limitations, such as induction of resistance and/or poor biological half-life, which reduce their clinical efficacy. To overcome these limitations several strategies have been explored. Chemical modification by the attachment of lipophilic moieties to (deoxy)nucleoside analogs should enhance the plasma half live, change the biodistribution and improve cellular Read More

Neopterin is produced by human and primate monocyte/macrophages upon activation by pro-inflammatory stimuli like Th1-type cytokine interferon-γ. Neopterin has pro-oxidative properties, which have been demonstrated in vitro in physicochemical and cell culture studies and also in in vivo experiments, e.g. the Langendorff perfusion model of rat hearts. In the past several years, the measurement of neopterin conce Read More

Chronic and acute overproduction of reactive oxygen species (ROS) under pathophysiologic conditions forms an integral part of the development of cardiovascular diseases (CVD), and in particular atherosclerosis. These ROS are released from different sources, such as xanthine oxidase, lipoxygenase, nicotinamide adenine dinucleotide phosphate oxidase, the uncoupling of nitric oxide synthase and, in particular, mitochon Read More

Coordinated and constructive physical activity is correlated with the maintenance of cognitive function in humans. Voluntary running also enhances neuroplasticity in adult and aging rodents, but the molecular pathways underlying these effects are still being elucidated. Considering the multifactorial nature of the biochemical links between physical activity and neurophysiology, it is likely that there are many pharmacolog Read More

During the transduction of extracellular signals within the cell, the stimulation of specific G protein-coupled receptors (GPCRs) can modulate adenylyl or guanylyl cyclase, phospholipase C activity and ion channels, which regulate second-messengers. These, in turn, trigger several biochemical cascades, including Ca2+ release, activation of protein kinases and gene expression. Significant changes of monoamine GP Read More

Endothelial cells (ECs) play a pivotal role in physiological and altered tissue neovascularization. They face multiple morphological, biochemical and functional changes during the different phases of angiogenesis, under the regulation of a great number of proangiogenic and antiangiogenic signals, including soluble and insoluble factors, cell-cell and cell-matrix interactions. ECs mutual contacts (and also interactions with othe Read More

For the development of new antiepileptics the kainate receptors, GluR6 and GluR5, are important targets. Based on the anticonvulsant effects of chinazolines and thieno[2,3-d]pyrimidines that are known from the literature, thieno[2,3-d][1.3]oxazines were synthesized and studied for their inhibitory properties at GluR6 and GluR5 receptors. The strongest inhibitor activity was observed with 5-methyl-6-phenyl-thieno[2,3-d][1. Read More

Superparamagnetic iron oxide nanoparticles can be used for numerous applications such as MRI contrast enhancement, hyperthermia, detoxification of biological fluids, drug delivery, or cell separation. In this work, we will summarize the chemical routes for synthesis of iron oxide nanoparticles, the fluid stabilization, and the surface modification of superparamagnetic iron oxide nanoparticles. Some examples of the Read More

Several hundreds of studies published the last decade have reported that α-lipoic acid (LA) possesses the potential to intervene in various therapeutically interesting pathways. However, it should be noted that LA reportedly exerts most of its effects at high micromolar concentrations; that amides of LA exhibit higher biological activity than the parent compound; and that molecular combinations (hybrids) obtained by co Read More

T lymphocytes bearing the γδ T cell receptor are known to play an important role in the first-line defense against viral, bacterial and fungal pathogens. Two main subsets of γδ T cells are known, showing distinct functional behavior: Vδ2 T lymphocytes, circulating in the peripheral blood, are involved in the response to mycobacterial infections and certain viruses, including coxsackie virus B3 and herpes simplex virus type Read More

Glycosaminoglycans (GAGs), such as heparin and heparan sulphate, are a class of linear, anionic polysaccharides that constitute the carbohydrate component of proteoglycans. The structure of GAG complexes with proteins can reveal details of their mechanisms of action in living systems and help to design new pharmaceuticals. Molecular modelling together with nuclear magnetic resonance (NMR) and other spectroscopic tec Read More