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Indole derivatives constitute an important class of therapeutical agents in medicinal chemistry including anticancer, antioxidant, antirheumatoidal, aldose reductase inhibitor, and anti-HIV agents. Reactive oxygen species are constantly generated in the human body and are involved in various physiologically important biological reactions. However, high levels of free radicals can cause damage to biomolecules such as lipids, proteins, and DNA within cells. Oxidative stress has been implicated in the development of neurodegenerative diseases like Parkinson's disease, Alzheimer's disease, Huntington's disease, epileptic seizures, stroke, and as a contributor to aging and some types of cancer. Indolic compounds are very efficient antioxidants, protecting both lipids and proteins from peroxidation and it is known that the indole structure influences the antioxidant efficacy in biological systems. Due to its free radical scavenger and antioxidant properties, synthesis of indole derivative compounds are under investigation to determine which exhibit the highest activity with the lowest side effects. Epidemiological studies have been strongly suggesting that antioxidants can decrease the rate of many diseases. However, more clinical studies are required to determine the efficacy and safety of these compounds. This chapter gives another perspective on antioxidant activities of synthetic melatonin analogues. [ABSTRACT FROM AUTHOR]

Among the four DNA bases, guanine, having the lowest redox potential, is the most susceptible to oxidation, and among the oxidized bases 7,8-dihydro-8-oxoguanine (8-oxoG) is certainly the lesion that has retained most attention over many years. This altered base can pair with A as well as C residues during replication. Eukaryotic cells use a specific DNA glycosylase, 8-oxoG DNA glycosylase (OGG1), to excise 8-oxoG from DNA, and repair-deficient cells are characterized by an increased G to T transversion frequency. It is essential that OGG1 has the ability to distinguish between 8-oxoG:C and 8-oxoG:A pairs and only removes 8-oxoG paired with C. This review will discuss the structural basis for OGG1 damage recognition and specificity as well as the literature on the biological consequences of OGG1 deficiency. [ABSTRACT FROM AUTHOR]

It is clear that UV sensitivity and high cancer susceptibility can be explained by defective DNA repair. However, many mutations in DNA repair genes result in multisystem disorders. Mutations in the same gene can result in different clinical outcomes and severity depending on the site of a mutation and the gene dosage. This is further complicated by the possibility of pleiotropic effects caused by disturbances in other cellular processes. While not discussed here, attempts to recapitulate the human genotype-phenotype relationships using transgenic mice are providing valuable insights into these disorders. It may soon be possible to determine a patient's clinical prognosis by analyzing the site of the mutation in the affected gene. [ABSTRACT FROM AUTHOR]