Mini Reviews in Medicinal Chemistry - Volume 7, Issue 10, 2007

Glioblastoma multiforme (GBM) is a highly malignant brain tumor. The interconvertible bioactive sphingolipids sphingosine-1-phosphate (S1P) and ceramide have profound effects on GBM cells, with ceramide causing cell death and S1P leading to cell survival, proliferation and invasion. This review will examine the effects of ceramide and S1P on glioma cells and the therapeutic potential of these pathways.

Sortase enzymes are attractive targets for the development of new anti-infective agents against Gram-positive pathogens because they covalently anchor virulence factors to the cell wall. Here we review what is known about the mechanism of sortase mediated protein anchoring and discuss recently identified inhibitors of this new important enzyme family.

Senile plaques in the brain of patients with Alzheimer's disease mainly consist of aggregates of amyloid β peptides (Aβ42, Aβ40). Aβ42 is more neurotoxic than Aβ40. This review describes recent findings from a structural analysis of Aβ42 aggregates and discusses their relevance to neurotoxicity through the formation of radicals.

The transport mechanism-based molecular design strategy would provide an effective tool for rationalized chemotherapy against tumors. To develop a platform for molecular modeling to circumvent multidrug resistance, we established new methods of high-speed screening for human ABCG2-drug interactions, quantitative structure-activity relationship (QSAR) analysis, and quantum chemical calculation for lead optimization.

Cell-based biosensors represent the next revolution in medical diagnostics, offering a number of significant advantages, such as high speed, portability and low cost. The present review focuses on the most successful technologies used for the detection of ultra-low concentrations of bioactive analytes (such as metabolic markers and pathogens) in clinical samples.

After nitrogen, fluorine occupies the position of second favorite heteroelement in life science-oriented research. In contrast, the trifluoromethoxy group is still perhaps the least well understood fluorine substituent, although its occurrence has significantly increased in the recent years. Today, significant application areas for trifluoromethoxy substituted pharmaceuticals are in the field of analgesics, anesthetics, cardiovascular Read More

DNA damage induces apoptosis of cells of hematological origin. Apoptosis is also widely believed to be the major antiproliferative mechanism of DNA damaging anticancer drugs in other cell types, and a large number of laboratories have studied drug-induced acute apoptosis (within 24 hours) of carcinoma cells. It is, however, often overlooked that induction of apoptosis of carcinoma cells generally requires drug concent Read More

Cysteine proteases selectively catalyze the hydrolysis of peptide bonds. Uncontrolled, unregulated, or undesired proteolysis can lead to many disease states including emphysema, stroke, viral infections, cancer, Alzheimer's disease, inflammation, and arthritis. Cysteine proteases inhibitors thus have considerable potential utility for therapeutic intervention in a variety of disease states. This review emphasizes on the new de Read More

Chondroitin sulfate (CS) is a complex carbohydrate polymer with variable sulfation which impacts function. CS exhibits a wide range of biological activities. Many experimental and clinical data are available, affirming that CS represents an effective and safe symptomatic treatment of osteoarthritis (OA) with delayed and sustained effects.

Depsipeptide (FK228), a new histone deacetylase inhibitor, has been recently introduced into clinical trials. This agent shows interesting metabolic properties, novel mechanism of action, and is undergoing phase I-II clinical studies in hematopoietic malignancies and solid tumors. Mechanism of action, pharmacokinetics and anticancer activity of depsipeptide is the subject of this review.

Cyclin-dependent kinase 5 (Cdk5) is a serine/threonine protein kinase, which forms active complexes with p35 or p39 expressed predominantly in neurons. Cdk5 is indispensable for the development of the central nervous system through regulation of neuronal migration. In mature neurons, Cdk5 has been implicated in various signaling transduction pathways, which contribute to functional neuronal activity. It has been widely Read More

The functions of melatonin, the hormone of the pineal gland, are of considerable current interest. Synthetic melatonin analogues as agonists and antagonists have been explored in some detail and the molecule can be considered as consisting of an indole core, acting mainly as a spacer, and the 5-methoxyl and 3-amidoethyl side chains acting as the functional components, as originally proposed by Heward and Hadley. This re Read More