Current Medicinal Chemistry - Volume 10, Issue 24, 2003

Ingold reviews the role of charge in reactions of alkylperoxyl radicals and superoxide with DNA and other biopolymers, a topic which has received scant attention. The abilities of the peroxyl radicals to attack polyanion DNA are controlled by Coulombic forces with only the positively charged ones being able to induce cleavage. Although the anionic and neutral radical counterparts do not directly cause DNA scission, they appe Read More

The role of electrostatic forces in free radical biology is very important but it is all too often overlooked. The radicals discussed in this review include positivelycharged, negatively-charged and neutral water-soluble alkylperoxyls and superoxide. Important scientific insights have been gained by generating these radicals in known quantities by the thermal decomposition of simple, “clean”, chemical precursors in the presence of p Read More

Reactive oxygen species (ROS) are produced continuously in living cells as a by-product of respiration and other metabolic activity. Some ROS may react with DNA, and in some cases may abstract an electron from the double helix, leading to long range electron transfer (ET) reactions. Thus, the DNA of living cells may be in a continuous state of ET. We consider here whether acridine-based anticancer or antimicrobial drugs, which Read More

In addition to synapse loss, neurofibrillary tangles, and neurodegeneration, oxidative stress and amyloid β-peptide [Aβ] deposition are hallmarks of Alzheimer's disease [AD] brain. Our laboratory coupled these two characteristics of AD into a comprehensive model to account for the synapse loss and neurodegeneration in AD brain. This model combines much of the extant studies on AD and is based on oxidative stress associated Read More

Cessation of blood flow to the liver is required during liver transplantation and resectional surgery. A growing body of experimental evidence suggests that restoration of blood flow to the ischemic liver initiates hepatocellular injury which may lead, in some cases, to severe liver injury and graft failure. A large number of studies have implicated reactive oxygen species as potential mediators of post-ischemic tissue injury. Re Read More

Numerous pathophysiological disorders involve some element of oxidative stress and bioenergetic deficit. Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors have been used recently as a promising new therapeutic strategy aimed at halting the bioenergetic decline associated with oxidative brain insults and other conditions. PARP-1 uses NAD+ as a substrate and is activated during stressful circumstances, mainly in the nucle Read More

Prostate cancer (PC) has become the most frequently diagnosed neoplasm and the second leading cause of cancer-related mortality in men. Its incidence rate has continued to increase rapidly during the past two decades, especially in men over the age of 50 years as they are living longer. The prostate in aging males is highly susceptible to benign and malignant proliferative changes. About two / thirds of all cancers, howev Read More

This review treats the mechanism of nitric oxide, catecholamines, and glutamate as important neurotransmitters and as neurotoxins, based on involvement of reactive oxygen species (ROS) and electron transfer (ET). ROS and ET can serve as a unifying framework for both transmission and toxicity, with ROS concentration being a crucial issue. Cell signaling, electrochemistry, antioxidants, and apoptosis are also discussed.

Evidence indicates that nerve gas toxins operate in ways in addition to inhibition of acetylcholine esterase. Alternative bioactivities are discussed with focus on electron transfer. The main class, including pralidoxime (2-PAM), incorporates conjugated iminium and oxime moieties that are electron affinic. Various physiological properties of iminium and oxime species are reviewed. The organophosphates encompass both ne Read More

Gossypol, a constituent of cottonseeds, displays various drug properties, including antifertility and anticancer. Toxicity is shown against the reproductive system, heart, liver, and membranes. The compound exhibits pro- and anti-oxidant behavior. Electron transfer (ET) functionalities, present in gossypol and its metabolites, comprise conjugated dicarbonyl, a quinone derivative, Shiff bases, and metal complexes. The pa Read More

Cannabinoids comprise three classes of compounds, the active components of marijuana (Cannabis sativa), as well as endogenous and synthetic derivatives. To date, two distinct cannabinoid receptors (CB1 and CB2) have been discovered, but evidence for further receptor types has been brought forward. The potential use of cannabinoids for medicinal purposes has long been known, but the mechanisms of action of both Read More

The development of the first automated oligosaccharide synthesizer, along with new methods for screening carbohydrate ligand arrays is likely to lead to a rapid acceleration in both our ability to synthesize these molecules, and understand the roles of oligosaccharides and glycoconjugates in biology. Consequently we may uncover new avenues for therapeutic intervention more rapidly. These recent developments are very imp Read More