Quinone Roles in NO Reduction & Production Enhancements & Tumor-Targeted Toxicity

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Quinones are important compounds used in antitumor therapy and other human illnesses. The common feature of these compounds is that these are prone to be reduced either chemically or enzymaticafly in biological media to produce reactive intermediates and products. Although efforts have been made in correlating redox potentials of these compounds with cytotoxicity, very little is known on how the environment affects the extent of production of reactive intermediates or products of these compounds in the presence of biologically relevant reducing agents. Our major aim is to understand the interrelated roles of environment and structure of these compounds and their intermediates, the semiquinones, in determining the extent of production of reactive oxygen and nitric oxide intermediates. By knowing this, an understanding of the cytotoxic action of these can be obtained and the design of more efficient drugs based on these types of compounds can be developed. Since semiquinone stabilization increases the rate of oxygen consumption in the presence of reducing agents we will now be studying the effect of metal chelation in orthosemiquinone stabilization and oxygen consumption. In contrast to previous years, and since the recognized most important macromolecule in determining both the formation and dead of tumor cells is the DNA molecule, we have now shifted our attention to DNA damaging reactions by cationic, neutral and anionic quinones in the presence and absence of reducing agents, and in the presence and absence of oxygen. Quinones are known to be reduced to the one-electron intermediate, the semiquinone, with the consequent production of reactive oxygen radicals after electron transfer to oxygen. In addition, semiquinones could also reduce nitric oxide to the nitrosyl ion with the consequent toxicity of this species.