Antoxis                                                             Targeting Free Radicals in Disease
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Free Radicals, Antioxidants and Disease Free radicals are atoms or molecules that contain an unpaired electron. This attribute confers a unique chemistry that can result in severe damage to biomolecules and cells. Under normal physiological conditions free radicals, known as reactive oxygen species, are continually produced at low level in all aerobic organisms. Protection is afforded by an elaborate defence system of which the dietary antioxidants, vitamins E and C, play an essential role. Respectively, these compounds annihilate radical species in lipid and aqueous environments by hydrogen atom transfer processes. However, there is substantial evidence that in many clinical conditions abnormally-high free radical loads are generated that overwhelm the endogenous antioxidant defences. The resultant damage, whether directly to the cell or by disruption of biochemical pathways, can contribute to the disease process itself. Examples are: Reperfusion injury that occurs when tissue is re-oxygenated following disruption of blood-flow. This includes acute ischaemic stroke, myocardial infarction and organ transplantation Neurodegenerative conditions such as Alzheimer’s disease and Parkinsons Autoimmune disorders Inflammatory processes Radiation exposure and therapy Antioxidant intervention, alone or in combination with conventional treatments, presents a realistic strategy to improve clinical outcomes. The use of dietary antioxidants in this context has, however, met with limited success. Consequently, there is considerable requirement for the rational design of high-potency therapeutic agents that are targeted to sites of radical production and attack, and that can effectively cross the blood-brain barrier. Antoxis will drive forward novel molecular design concepts and commercialise drug candidates in this potentially lucrative, and as yet untapped, therapeutic area.   Our Technology Flavonoids are a large group of polyphenolic phytochemicals that are found in many foods and beverages. Epidemiological studies have suggested that consumption of diets high in such compounds is protective against heart disease and certain cancers, an effect ascribed to an antioxidant role. The biological activity of these compounds have been a source of intense research by many groups world-wide over the last decade and beyond. From our intimate knowledge of the structure-function relationship of natural, phytochemical antioxidants, we have rationally designed the Antoxis AO-1 family of compounds. These new chemical entities display dual functionality, uniquely combining exceptional antioxidant potency with a targeting platform to ensure rapid delivery into key cellular compartments at risk of free radical damage and known to be involved in neurodegeneration. In commissioned studies using cortical neuron cell cultures, our compounds were found to be significantly protective in models of free radical stress and reperfusion damage that occurs in ischaemic stroke. Indeed lead compounds demonstrated reductions in cell death by up to 67%. Critically, the results have validated our informed design approach. We are now entering in-vivo stroke trials with our lead candidate. Capitalising on its growing structure-activity knowledge base, Antoxis is currently expanding its pipeline and IP with the introduction of the AO-2 family of compounds.