Modeling Natural Anti-Inflammatory Compounds by Molecular Topology

One of the main pharmacological problems today in the treatment of chronic inflammation diseases consists of the fact that anti-inflammatory drugs usually exhibit side effects. The natural products offer a great hope in the identification of bioactive lead compounds and their development into drugs for treating inflammatory diseases. Computer-aided drug design has proved to be a very useful tool for discovering new drugs and, specifically, Molecular Topology has become a good technique for such a goal. A topological-mathematical model, obtained by linear discriminant analysis, has been developed for the search of new anti-inflammatory natural compounds. An external validation obtained with the remaining compounds (those not used in building up the model), has been carried out. Finally, a virtual screening on natural products was performed and 74 compounds showed actual anti-inflammatory activity. From them, 54 had been previously described as anti-inflammatory in the literature. This can be seen as a plus in the model validation and as a reinforcement of the role of Molecular Topology as an efficient tool for the discovery of new anti-inflammatory natural compounds

Systemic zinc redistribution and dyshomeostasis in cancer cachexia

Cachexia affects up to two thirds of all cancer patients and is a significant cause of morbidity and mortality. It is a complex metabolic syndrome associated with the underlying illness and characterized by loss of skeletal muscle tissue with or without loss of fat mass. Cachexia’s other prominent clinical symptoms include anorexia, systemic inflammation, pediatric growth failure, and hypogonadism. The relationship between the symptoms of cancer cachexia and the underlying illness is unclear, and there is an urgent need for a better understanding of the pathophysiology of this syndrome. Normal Zn metabolism is often disrupted in cancer patients, but the possible effects of systemic Zn dyshomeostasis in cachexia have not been investigated. We propose that the acute phase response can mediate Zn redistribution and accumulation in skeletal muscle tissue and contribute to the activation of the ubiquitin–proteasome pathway that regulates protein catabolism. This chronic redistribution deprives Zn from other tissues and organs and compromises critical physiological functions in the body. The cardinal symptoms of Zn deficiency are anorexia, systemic inflammation, growth failure in children, and hypogonadism. These symptoms also prominently characterize cancer cachexia suggesting that the role of systemic Zn dyshomeostasis in cachexia should be investigated

A biochemical investigation of auranofin nephrotoxicity by high field proton nuclear magnetic resonance spectroscopy

High-field proton NMR spectroscopic analysis of urine and plasma has been employed to study the biochemical effects and nephrotoxic action of an intramuscular dose of auranofin in rats. Auranofin induced a characteristic profile of proximal tubular damage as evidenced by aminoaciduria, lactic aciduria and increased urinary acetate concentrations. In addition, ethanol was detectable in both urine and plasma obtained from auranofin-treated rats. Auranofin-mediated elevations in the plasma and urine concentrations of 3-D-hydroxybutyrate indicated an increased utilisation of fats for fuel in rats treated with this novel therapeutic agent