Mini Reviews in Medicinal Chemistry - Volume 11, Issue 2, 2011

There is a growing consensus that cellular immune responses are associated with the clinical outcome of hepatitis C virus infection (HCV). The development of Tetramer staining, ELISpot, flow cytometry and epitope mapping technologies makes it possible to enumerate, phenotype and assess the proliferation and function of HCV specific T cells; as well as map and predict T cell epitopes and track the evolution of T cell epitopes. Such information is essential for the development of effective therapeutic and prophylactic HCV vaccines. This article summarizes the technical advances relevant to HCV specific T cell responses.

Small interfering RNA (siRNA) has become a specific and powerful tool to turn off the expression of target genes, and has turned into a promising tool in molecular medicine. It can be targeted against cancer by several strategies. These include the suppression of overexpressed oncogenes, retarding cell division by interfering with cyclins and related genes or enhancing apoptosis by inhibiting anti-apoptotic genes. RNA interference (RNAi) against multidrug resistance (MDR) genes or chemo/radio-resistance and angiogenesis targets may also provide beneficial cancer treatments. Successful cancer therapy by siRNA in vitro and in vivo provides the enthusiasm for potential therapeutic applications of this technique. Here, we review RNAi in cancer therapy, highlighting recent progress and examining the hurdles that must be overcome before this promising technology is ready for clinical use.

The oceans are a source of combinatorial library of unique natural products, ‘not found in the terrestrial environment’. Marine invertebrates such as sponges, molluscs, bryozoans, tunicates (Urochordata) and their associated microorganisms are the major representatives of promising bioactive compounds. Among these, the predatory molluscan cone snails have evolved with highly structured small and complex array of peptides (more than 50,000) linked to their prey capture and defence. These peptides have become a valuable source of neuro pharmacological targets as many of them selectively modulate ion channels and transporters. A group of scientists from United States, Europe, Australia, Israel and China has characterized drugs for neuropathic pain and pharmacological targets from the peptides of a few cone snail species. Several are now in clinical and preclinical development. Less than 1% of the cono peptides are pharmacologically characterized. India has a diversity of 20-30% of total cone snail species distributed worldwide. A group of Indian Scientists has made promising drug discovery programs from Conus peptides. This review will focus on the Conus peptides from Indian cone snails species, their neuro pharmacological targets and future directions.

Blood platelets play a crucial role in the primary hemostasis and vessel wall repair. However; platelet hyperactivation is implicated in the pathogenesis of cardiovascular diseases such as thrombosis, atherosclerosis and stroke. Epidemiological data have suggested that regular consumption of fruits and vegetables, which are rich in flavonoids, is associated to a reduction in cardiovascular events. The cardioprotective effect of flavonoids is partly due to the inhibition of platelet function. However; the mechanisms underlying the anti-platelet effect of these compounds remain unclear. The aim of this review is to discuss the role of platelets in cardiovascular disease and to provide an overview of the potential anti-platelet effect of flavonoids, focusing on the various platelet signaling pathways modulated by flavonoids, including oxidative stress, protein tyrosine phosphorylation, calcium mobilization and nitric oxide pathway. The understanding of these mechanisms will be helpful in the development of new anti-platelet agents based on flavonoids with fewer or no adverse effects.

Histamine, a low molecular weight amine has been extensively studied for its various pharmacological profiles. Until recently histamine was thought to act on three receptors - H1, H2 and H3. Merely a decade back, sequencing of human genome has revealed a new histamine receptor - H4 receptor. This 390 amino acid sequenced receptor has around 38% homology with histamine H3 receptor besides; the pharmacological profile of the protein is quite different from other histamine receptors. H4 receptor is mainly expressed in mast cells and leukocytes and involves various physiological functions related to inflammation and allergy. Potent selective H4 receptor agonists and antagonists have been synthesized and in vivo studies have indicated their action on H4 receptor. In this review, structure, expression, homology sequence of H4 receptor among the different species have been documented. Further, structure activity relationship (SAR) of H4 and ligands on the basis of their nucleus has been discussed in depth. In addition, anti-inflammatory effects of H4 receptor antagonists, with special emphasis to JNJ7777120, a selective H4 receptor antagonist have been focused exhaustively.

Plant endophytic fungi are an important and novel resource of natural bioactive compounds with their potential applications in agriculture, medicine and food industry. In the past two decades, many valuable bioactive compounds with antimicrobial, insecticidal, cytotoxic, and anticancer activities have been successfully discovered from endophytic fungi. During the long period of co-evolution, a friendly relationship was formed between each endophyte and its host plant. Some endophytes have the ability to produce the same or similar bioactive compounds as those originated from their host plants. This review mainly deals with the research progress on endophytic fungi for producing plant-derived bioactive compounds such as paclitaxel, podophyllotoxin, camptothecine, vinblastine, hypericin, and diosgenin. The relations between endophytic fungi and their host plants, biological activities and action mechanisms of these compounds from endophytic fungi, some available strategies for efficiently promoting production of these bioactive compounds, as well as their potential applications in the future will also be discussed. It is beneficial for us to better understand and take advantage of plant endophytic fungi.

Flavonoids are a group of polyphenolic compounds, diverse in chemical structure and characteristics, found ubiquitously in plants. Until now, more than 9000 different flavonoid compounds were described in plants, where they play important biological roles by affecting several developmental processes. There has been increasing interest in the research of flavonoids from dietary sources, due to growing evidence of the versatile health benefits of flavonoids including anti-inflammatory, antioxidant, antiproliferative and anticancer activity, freeradical scavenging capacity, antihypertensive effects, coronary heart disease prevention and anti-human immunodeficiency virus functions. This paper reviews the current advances in flavonoids in food with emphasis on mechanism aspects on the basis of the published literature, which may provide some guidance for researchers in further investigations and for industries in developing practical health agents.

Assessing modifiable risk factors for metabolic and cardiovascular diseases prior to the onset of disease could allow effective prevention initiatives. Equally, monitoring in diabetic people glucose, haemoglobin A1c, ketones, lipid profiles, and urinary microalbumin concentrations allows the prevention, early detection, and treatment of diabetes-related acute and chronic complications and has a positive impact on the process of care in the management of patients with diabetes. The point-of-care testing (PoCT) technology offers convenient aspects: immediate results, decision-making without the need for repeated visits, use of fingerstick blood samples. More patients could be identified at early stages of their disease/ complication provided that pre-analytical, analytical, and post-analytical errors are minimised. Indeed, prediction requires instruments with proved precision, accuracy, validity, and reliability. Reference laboratory services are now available to manufacturers so to confirm PoCT results. There are several PoC devices on the market that may allow for “real time” screening, diagnosis, and monitoring in diabetes care. Tight glucose control has a key role in long-term health of diabetic people and in the primary prevention of diabetic chronic complications. Diabetic patients are currently educated to control capillary glucose levels daily in order to maintain them within target limits. Blood glucose meters are widely used not only by diabetic patients to self-manage their disease but also by physicians to monitor critically ill patients. Glycated haemoglobin A1c can now be measured with fast and easy automated PoCT instruments to monitor long-term serum glucose regulation. Urinalysis dipsticks and blood betahydroxybutyrate meter allow measuring urine and blood ketones to prevent ketoacidosis. Since the routine measurement of urinary albumin has been suggested in diabetes mellitus as a predictor of overt diabetic nephropathy, semi-quantitative visual dipsticks and quantitative automated methods of urine testing became available for bedside detection of urine albumin at low concentrations and for the determination of the microalbumin creatinine ratio. While the National Cholesterol Education Program recommends that all adults aged 20 years and over have their blood cholesterol checked at least once every 5 years, adult diabetic patients should measure fasting lipid profile at least annually or every two years in case of low-risk lipid values. There are PoCT devices on the market that provide a full lipid panel (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides). The overview summarises current state-of-the-art of PoCT in diabetes care.