Mini Reviews in Medicinal Chemistry - Volume 7, Issue 2, 2007

myo-Inositol monophosphatase has long been a target for drug discovery. Recent work has given detailed insight into its mechanism and dynamics plus new activities and some novel series of inhibitors. The goal of a bio-available inhibitor for this enzyme, however, remains a major challenge for medicinal chemistry.

Exhaled breath analysis for clinical diagnosis and therapeutic monitoring is described with special reference to the techniques used and the underlying chemistry and physics involved. Brief outlines are given of the research carried out to date, and prospects for the future of this potentially valuable non-invasive technique are indicated.

Various classes of cytotoxic compounds which alkylate cellular thiols are described namely α, β-unsaturated ketones, α-methylene-γ -lactones, azines of Mannich bases, imexon, isothiocyanates, a benzoacronycine as well as activation by thiols prior to alkylation. The mechanisms of action of some of the molecules, such as the formation of reactive oxygen species, are presented. The cytotoxicity of a number of drugs can be i Read More

Amyotrophic lateral sclerosis (ALS) is a clinically severe and fatal neurodegenerative disease characterized by a loss of both upper and lower motor neurons, resulting in progressive muscle loss and paralysis. While the exact cause of neuronal death in ALS remains unknown, it is proposed that multiple molecular defects trigger motor neuron cell death. These pathophysiological mechanisms include oxidative stress, mitochondri Read More

Association of proteins into homo- and hetero-oligomers plays an important role in a plethora of biological phenomena. Inhibition of these interactions is increasingly recognized as a valuable new direction in drug design. In this mini-review we consider inhibition of protein misfolding and aggregation, molecules that disrupt enzyme quaternary structure, and signaling inhibitors, as emerging drugs.

Cholera Toxin (CT) recognizes the cell membrane through specific interactions with ganglioside GM1. Recent structural elucidation of the CT/GM1 complex has allowed the rational design of artificial receptors for the toxin, which could function as anti-cholera drugs. The efforts towards the rational design of Cholera Toxin inhibitors will be presented.

There is considerable evidence showing that oxidative damage is one of the earliest neuronal and pathological changes of Alzheimer disease and many, if not all, of the etiological and pathological causes of the disease are related, directly or indirectly, to free radical production and oxidative damage. Here we summarize the current body of knowledge suggestive that oxidative damage is, if not the key factor, certainly a major Read More

The existing chemical data such as those created by high throughput screening (HTS), structure-activity relationship (SAR) studies are converted into information as a result of storage and registration. Accessibility, manipulation, and data mining of such information make up the knowledge for drug development. Cheminformatics, exploiting the combination of chemical structural knowledge, biological screening, and data minin Read More

Chronic myelogenous leukemia (CML) is a myeloproliferative disease characterized by the presence of the Philadelphia chromosome that expresses the constitutively activated tyrosine kinase Bcr-Abl; this enzyme causes hyperproliferation of the stem cells and the consequent pathology of the disease. Targeted inhibitors of Bcr-Abl have antiproliferative effects on the leukemic cells and induce apoptosis, favouring a regression of Read More

Cisplatin is routinely employed for the treatment of testicular, ovarian cancer and head/neck tumors. Typical doses administrated to patients are 100 mg/day for up to five days. It is believed that the mechanism of action appears to be the binding of cis-Pt(NH3)2 unit to DNA at two neighboring guanine bases. In the years following the introduction of cisplatin, the design of new platinum anticancer drugs concentrated mainly on Read More