Current Medicinal Chemistry - Volume 13, Issue 7, 2006

Recent advances in our understanding of cellular and molecular mechanisms of viral penetration of the target cell have provided the basis for novel chemotherapy and prophylaxis of HIV-1 infections. This knowledge has been successfully applied to the development of inhibitors that target discrete steps of the entry process. Interesting approaches for prevention of HIV-1 entry include the use of small-molecule inhibitors, na Read More

The ubiquitin-proteasome proteolytic pathway plays a major role in selective protein degradation and regulates various cellular events including cell cycle progression, transcription, DNA repair, signal transduction, and immune response. Ubiquitin, a highly conserved small protein in eukaryotes, attaches to a target protein prior to degradation. The polyubiquitin chain tagged to the target protein is recognized by the 26S proteaso Read More

Sphingolipids constitute a broad class of compounds with many biological functions. The sphingolipid metabolites ceramide and sphingosine are potent apoptosis inducers and produce cell cycle arrest, whereas sphingosine-1-phosphate promotes cellular growth and differentiation. Herein, the effects of sphingolipids and their analogs on diverse signaling pathways implicated in the apoptotic process are highlighted. The relativel Read More

Reduced circulating levels of high density lipoprotein cholesterol (HDL-C) are a frequent lipoprotein disorder in coronary heart disease patients and can be caused by either genetic and/or environmental factors (sedentary lifestyle, diabetes mellitus, smoking, obesity or a diet enriched in carbohydrates). Extremely low serum HDL-C levels occur in patients with Tangier disease (TD), which is caused by mutations in the aden Read More

The recent discovery that members of the vascular endothelial growth factor (VEGF) family of secreted glycoproteins can mediate lymphatic vessel growth (lymphangiogenesis) via cell surface receptor tyrosine kinases expressed on endothelial cells has opened the way for therapeutic intervention for pathologies involving dysregulated lymphatic vessel function. At least two members of this family, VEGF-C and VEGF-D, Read More

Human P-glycoprotein (P-gp, ABCB1) plays an important role in the development of resistance to anticancer therapy. This ABC-transporter (ATP-binding cassette transporter) intercepts drugs at the level of the plasma membrane and effluxes them before they are able to reach their intracellular target structures. Inhibition of P-gp by low molecular weight compounds has been advocated as a concept for resensitizatio Read More

Our interest has been centered on isoquinoline alkaloids obtained from Argemone mexicana (Papaveraceae), Aristolochia constricta (Aristolochiaceae) and the opium alkaloid, papaverine. In this respect, the effect of these isoquinoline alkaloids was investigated on contractions induced by naloxone of isolated guinea pig ileum acutely exposed to morphine in vitro. The activity of these alkaloids was compared to t Read More

Nature continues to be the main source of inspiration for synthetic chemists in their quest to make novel conjugates, which can have different physical, biological and medicinal properties. Nature makes these conjugates from mixed biosynthesis and some of these chimeras are found to exhibit unusual biological properties. During the past two decades design of such entities has been receiving increasing attention. Amon Read More