Mini Reviews in Medicinal Chemistry - Volume 8, Issue 8, 2008

The marine environment has been shown to be the source of a great diversity of chemical structures with promising biological activities. The isolation, biological evaluation, chemical properties and synthetic elaborations of the products of marine organisms and microorganisms have attracted the attention of organic chemists, medicinal chemists, biologists and pharmacists. Marine organisms and microorganisms have provided a large proportion of the natural antiinflammatory products over the last years. Marine organisms include green algae, brown algae, red algae, sponges, coelenterates, bryozoans, molluscs, tunicates, echinoderms, miscellaneous marine organisms and marine microorganisms and phytoplankton. This review describes current progress in the development of a selection of new anti-inflammatory agents from marine sources. The chemistry and biological evaluation are discussed.

Inhibitors of c-jun-N-Terminal Kinase (JNK) have many potential therapeutic indications ranging from neurodegenerative disease, to metabolic disorders, inflammation, cardiovascular disease, and cancer. This overview will highlight biological inhibitors such as JNK-interacting protein (JIP) as well as small molecule inhibitors from various structural classes including, aminopyrimidines and indazoles.

Subjects with nonalcoholic fatty liver disease are at risk of progressive liver failure. Lifestyle changes including weight-loss strategies and increased physical activity remain the first-line approach, but a few pharmacological treatments have also been successfully tested. Several drugs improve biochemistry, only a few improve histology; in all cases, the results were not sustained after treatment stop. Pharmacological treatment is not so far indicated outside controlled clinical trials with histological outcomes.

Recently, Canadian, US and European health regulatory agencies issued warnings about an increased risk of stroke and death in elderly patients with dementia receiving atypical antipsychotics. Assessing both randomised and nonrandomised evidence, this systematic review found conflicting findings, particularly for risperidone. More research is needed to better inform clinical practice.

Nucleic acids catalyse the conversion of α-helical prion protein to the β-structured protein oligomers and amyloids structurally similar to the infectious isoform of protein. Simultaneously, the prion protein, similar to gene regulating proteins, bends, unwinds and condenses nucleic acid. These properties might be related to the biological function and prion infection.

Antibiotic resistance nowadays plays an important role in the treatment of uncomplicated and complicated urinary tract infections (UTIs). In uncomplicated UTI efforts are made to use antibiotic substances exclusively for this indication. In complicated UTI substances with activity against bacteria harbouring common resistance mechanisms are investigated. Additionally pharmacokinetic/ pharmacodynamic parameters are used to improve dosing strategies.

Nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor is a candidate target for novel therapeutics for a range of conditions, including obesity. This article reviews recent advances in understanding of N/OFQ's involvement in the regulation of food intake and appraises current developments in the rational design of antagonists aimed at the NOP receptor.

Non-selective cationic channels (NSCC) are a heterogeneous family of channels, widely expressed in nonexcitable and excitable cells, that share several functional characteristics but have diverse molecular origin. NSCC can be formed by transient receptor potential (TRP) channels, calcium activated non-selective channels, hyperpolarization activated cation currents, acid-sensitive cationic channels (ASIC), etc. As a result of its wide expression, as well as to the fact that the activation of such currents produce a persistent membrane depolarization, NSCC have been involved in a variety of neuronal processes such as signal transduction, firing pattern (including plateau potentials and bursting mechanisms) as well as synaptic transmission. Due to the relevance of such channels, alterations in their normal function have been associated with the pathophysiology of several nervous system diseases. Over the last years several blockers of such channels have been discovered. Here we review the pharmacology of NSCC blockers including trivalent cations, verapamil derivates, flufenamic acid, the “typical” TRP blockers 2-APB, ACA and SKF 96365 as well as ASIC blockers. This review focuses on the pharmacological properties of such drugs and their potential use for the understanding of the nervous system as well as for the treatment of neurological diseases.

Disturbances of endothelin production or clearance contribute to the pathophysiology of several cardiovascular diseases including Chagas disease cardiomyopathy caused by the protozoan Trypanosoma cruzi. In rats, endothelins contribute to control the acute phase, probably by stimulating nitric oxide production. We point out the necessity for new studies to better evaluate high levels of endothelin in the course of other infectious diseases, for which only its detrimental effects have been emphasized.

Hypertension is a common and progressive disorder that possesses a major risk for cardiovascular and renal disease. Recent data have revealed that the global burden of hypertension is an important and increasing public health problem worldwide and that the level of awareness, treatment and control of hypertension varies considerably among countries. Hypertension is often called a ‘silent killer’ because persons with this pathological condition can be asymptomatic for years and then have a fatal heart attack or stroke. The field of naturally occurring antihypertensive agent is a research area rapidly expanding due to the high potential of such molecules as new antihypertensive drugs. Recently, a great number of plant-derived substances have been evaluated as possible antihypertensive agents through different mechanisms of action such as alkaloids, flavonoids and terpenoids. In this mini-review we will discuss the medicinal chemistry of these compounds.