Mini Reviews in Medicinal Chemistry - Volume 6, Issue 2, 2006

Probing for Antiparasitic Drugs Every person on earth is infected by at least several parasites. The most dangerous parasites are transmitted by vectors and cause the death of millions annually. In order to reduce mortality resulting from such infections there is a need to interrupt the life cycle of the parasites. A parasitic disease will not be eradicated unless efforts to contain it below a "critical mass" succeed. The critical Read More

Resistance to anti-leishmanial drugs is a mounting problem in high-endemicity regions of South Asia and, potentially, in the context of HIV-Leishmania coinfections in Southern Europe. The molecular basis for clinical drug resistance is still largely unknown. It is important, however, to identify all relevant drug resistance markers for further drug development and for epidemiological surveys. An elegant and powerful me Read More

Many similarities exist between cancer cells and parasites. A potentially lucrative starting point for the discovery of novel drugs to combat parasites is to examine available compounds developed against cancer for antiparasitic properties. Here, we review the use of current and promising anticancer agents for treating major human parasitic diseases.

The leishmaniases consist of visceral and cutaneous syndromes present in > 30 endemic regions of the world. Miltefosine (hexadecylephosphocholine) is the first oral agent that is effective and tolerated for both visceral and cutaneous disease in several endemic regions, and represents a major advance in the treatment of these diseases.

The clinical treatment of leishmaniasis is based on a limited number of drugs, which are associated with adverse effects and have already induced resistance. Amphotericin B (AmB), a polyene antibiotic produced by Streptomyces sp, is the only anti-leishmanial drug which has not induced clinical resistance since its discovery in 1956. The limiting factor in the use of AmB is its toxic effects, mainly nephrotoxicity. The maxima Read More

Antimalarial drugs are urgently and continuously required. Parasite enzymes involved in antioxidant defence represent interesting target molecules for rational drug development. Here we summarize the currently available data on structural, biochemical, and functional properties of these proteins in an attempt to evaluate and compare their potential as drug targets.

Over 300 million cases of malaria each year cause significant morbidity and mortality. Growing drugresistance among the Plasmodia that cause malaria motivates the development of additional anti-malarial drugs. This review summarizes the current state of knowledge about potential drug targets for malaria. The recently sequenced malaria genome data clarifies parasite metabolic pathways, and more metabolic targets ha Read More

Wolbachia endosymbionts of filariae are targets for the development of new antifilarial chemotherapy. Doxycycline to deplete Wolbachia from the worm has demonstrated the feasibility of this strategy and has provided a new chemotherapeutic tool. Recent research shows that depleting Wolbachia will also lessen pathology, and lessen adverse reactions to traditional antifilarial drugs.

Free radicals may be reaction intermediates in biological systems in more situations than are presently recognized. However, progress in detecting such species by Electron Spin Resonance (ESR) has been relatively slow. ESR is a very sensitive technique for free radical detection and characterization. It can be used to investigate very low concentrations of radicals provided that they are stable enough for their presenc Read More

Thyrotropin releasing hormone (TRH: pyroglutamic acid-histidine-prolineamide) regulates the activity of cells in the anterior pituitary and within the central and peripheral nervous systems. TRH, which has been the subject of much research over the past three decades, exerts its effects by acting through class A G-protein coupled receptors. The recent discovery of a second receptor subtype has generated an interest in the Read More

Most solid tumors are angiogenesis dependent. Anti-angiogenic pharmaceuticals that inhibit the growth of new blood vessels offer considerable promise as anti-cancer agents. With increasing numbers of antiangiogenic drugs in clinical trials, there is an urgent need for detailed characterization of the heterogeneity of tumor vasculature and dissection of the complex network of mechanisms that control tumor an Read More

Oxidative stress plays an important role in the pathogenesis of asthma. Recently several investigators have studied the effects of a variety of antioxidants on asthma. Antioxidants, including L-2- oxothiazolidine-4-carboxylic acid, reduce airway inflammation and hyper-responsiveness of asthma and may be novel therapeutic agents for asthma.

Proteomics is becoming an important research area for studying protein expression patterns induced by different external stimuli. An important aspect of proteomics is to identify and quantify proteins. Many new technologies and techniques have been developed in this field and have been applied to various aspects of drug discovery.