DESIGN AND SYNTHESIS OF NOVEL SYNTHETIC ANTIOXIDANTS FOR THE TREATMENT OF OXIDATIVE STRESS RELATED DISEASES

Free radicals play an important role in many physiological processes that occur in the human body such as cellular defense responses to infectious agents and a variety of cellular signaling pathways. While at low concentrations free radicals are involved in many significant metabolic reactions, high levels of free radicals can have deleterious effects on biomolecules like proteins, lipids, and DNA. Many physiological disorders such as diabetes, ageing, neurodegenerative diseases, and ischemia-reperfusion (I/R) injury are associated with oxidative stress.1 In particular, the deleterious effects caused by I/R injury developed during organ transplantation, cardiac infarct, and stroke have become the main cause of death in the United States and Europe.1,2 In this context, we synthesized and characterized a series of novel indole-amino acid conjugates as potential antioxidants for I/R injury. The synthesis of indole-phenol conjugate compounds is also discussed. Phenolic derivatives such as caffeic acid, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), resveratrol, and its analogues are known for their significant antioxidative properties. A series of resveratrol analogues have been designed and synthesized as potential antioxidants. The radical scavenging mechanisms for potential antioxidants and assays for the in vitro evaluation of antioxidant activities are also discussed.

ACETYL RADICAL IN TOBACCO SMOKE: DETECTION, QUANTIFICATION AND SIMULATION

Free radicals are present in cigarette smoke and can have a negative effect on human health by attacking lipids, nucleic acids, proteins and other biologically important species. However, because of the complexity of the tobacco smoke system and the dynamic nature of radicals, little is known about the identity of the radicals, and debate continues on the mechanisms by which those radicals are produced. In this study, acetyl radicals were trapped from the gas phase using 3-amino-2, 2, 5, 5- tetramethyl-proxyl (3AP) on solid support to form stable 3AP adducts for later analysis by high performance liquid chromatography (HPLC), mass spectrometry/tandem mass spectrometry (MS-MS/MS) and liquid chromatography- mass spectrometry (LC-MS). Simulations of acetyl radical generation were performed using Matlab and the Master Chemical Mechanism (MCM) programs. A range of 10- 150 nmol/cigarette of acetyl radical was measured from gas phase tobacco smoke of both commerial and research cigarettes under several different smoking conditions. More radicals were detected from the puff smoking method compared to continuous flow sampling. Approximately twice as many acetyl radicals were trapped when a GF/F particle filter was placed before the trapping zone. Computational simulations show that NO/NO2 reacts with isoprene, initiating chain reactions to produce a hydroxyl radical, which abstracts hydrogen from acetaldehyde to generate acetyl radical. With initial concentrations of NO, acetaldehyde, and isoprene in a real-world cigarette smoke scenario, these mechanisms can account for the full amount of acetyl radical detected experimentally. This study contributes to the overall understanding of the free radical generation in gas phase cigarette smoke.