Mini Reviews in Medicinal Chemistry - Volume 9, Issue 5, 2009

Infectious diseases caused by bacteria, fungi, viruses and parasites are still a major threat to public health, despite the tremendous progress in human medicine. New antimicrobials are needed in medicine due to the rapid emergence of new resistant and opportunistic microbes and the increasing number of patients suffering from immunosuppressive situations, e.g., acquired immunodeficiency syndrome, transplantation, cancer, etc… Research on new antimicrobial substances must therefore be continued and all possible strategies should be explored. Plants have been a source of therapeutic agents from more than 5000 years. Approximately 25% of modern medications are developed from plants. In the area of infectious diseases, 75% of new drugs originated from natural sources between 1981 and 2002. As less than 10% of the world's biodiversity has been tested for biological activity, many more useful natural lead compounds are awaiting discovery. The Cistaceae family comprises a large number of species, growing in the warm temperate regions of the Mediterranean area, that have been and are still used as medicinal plants, particularly in folk medicine. In the present review, we analyse the past, present and future of medicinal plants of the Cistaceae family present in the Iberian Peninsula, both as potential antimicrobial crude drugs as well as a source of natural compounds that act as new anti-infectious agents.

Drugs which inhibit epidermal growth factor receptor (EGFR) are used in the treatment of cancers. EGFR may contribute to the development of hypertension by regulating vascular tone and renal Na+ handling. Synthetic EGFR inhibitors reduce blood pressure in some experimental models of hypertension suggesting that this receptor is a novel target for antihypertensive therapy.

Alzheimer's disease is a chronic and progressive neurodegenerative disorder. The presence of functional cannabinoid CB2 receptors in central nervous system (CNS) has provoked that this receptor and its agonist ligands are now considered as promising pharmacological targets for neurological diseases. Herein, we review the evidences supporting the potential role of the ECS as a therapeutic target, focused on CB2 receptor and its ligands, for the treatment of Alzheimer 's disease.

Every year about 7 million people die from of various types of cancer, making this disease responsible for 12.5% of deaths worldwide. Consequently, there is an overwhelming demand to develop new, more potent and effective, anticancer drugs. Natural products represent the most valuable source with inexhaustible reserves, in which the researchers work could identify novel active agents that may serve as the leads and scaffolds for transformation into desperately needed efficacious drugs. This paper is devoted to reviewing some of the most outstanding achievements in the application of natural products as models and precursors for anticancer agents published in the post 2000 literature. Particular emphasis is placed on the chemical modification of active principles isolated from natural products, in hope of obtaining the desirable derivatives for the treatment of different types of cancer, including pancreatic, gastric, breast, colon cancers and leukemia.

As an example of a multi-template approach, we focused on the 3,3-diphenylpentane (DPP) skeleton, which has been demonstrated to act as a steroid skeleton substitute. Various ligands for nuclear receptors (NRs), including vitamin D receptor (VDR), androgen receptor (AR) and farnesoid X receptor (FXR), and inhibitors of steroid metabolismrelated enzymes, including 5α-reductase and HMG-CoA reductase (HMGR), have been efficiently created by introducing various substituents onto the DPP skeleton.

Unlike the earlier agents in this class, certain of the newer histamine HB2B-receptor antagonists (so-called secondgeneration HB2B-receptor antagonists) have recently been reported to promote gastric mucosal defenses. We review herein the structure, specificity, and mechanisms of these agents with a special focus on their cytoprotective/gastroprotective actions.

Aim of the present review is to summarize the different evidences regarding the ability of cannabinoids to control new vessels formation, and in this way, to suggest new possible molecular targets for the development of drugs which may be helpful in the management of different pathological condition associated to angiogenesis.

A huge number of organophosphate poisonings occurring in agriculture, and a constant threat of misapplication of organophosphates as warfare agents require antidotes that efficiently improve the health-condition of intoxicated subjects. Pyridinium aldoximes are medically used to reactivate the cholinesterase enzymes inhibited by organophosphates. This paper outlines pharmacokinetics, metabolic disposition and blood-brain-barrier penetration of pyridinium aldoximes into the human and animal body, and the methods of their pharmacological analysis.

Nitric Oxide, which acts as a non-specific cytotoxic mediator and a biological messenger on immunological competence, has been gaining significantly increasing importance. As an alternative to conventional NSAIDs having significant side effects, pharmacologically improved and therapeutically enhanced NO releasing non-steroidal antiinflammatory drugs with less side effects are being planned to produce.

The anti-coagulant activated protein C (APC) can exert direct effects on cells, including cytoprotective functions involving apoptosis and inflammation mechanisms. These cytoprotective properties of APC require the presence of protease-activated receptor-1 (PAR-1) and endothelial protein C receptor (EPCR) resulting in inhibition of inflammatory gene expression and down-regulation of p53 and Bax. Several in vitro and animal studies have documented such cytoprotective properties of APC. The first evidence for a cytoprotective role of APC in a clinical setting came from the PROWESS trial in which APC administration reduced mortality rates in severe sepsis patients. However, although APC certainly has the potential to be used in a broader range of clinical settings it is thwarted by the associated risk of bleeding. Further research within this area towards improved therapeutics of specific APC mutants has taken place.

Proteome analysis, the key technology for biomarker discovery, continues to gain importance in clinical diagnosis and follow-up. In this review we describe proteome analysis in the context of allogeneic, hematopoietic stem cell transplantation concentrating on capillary electrophoresis coupled on-line to mass spectrometry.