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

醌在 NO 还原中的作用

• 批准号: 7288961
• 负责人: ANTONIO E ALEGRIA
• 金额: $ 20.13万
• 依托单位: UNIVERSITY OF PUERTO RICO AT HUMACAO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7288961
• 关键词: Affect; Attention; Biological; Charge; Consumption; DNA; DNA Binding; DNA Damage; DNA strand break; Electron Transport; Electrons; Environment; Equilibrium; Grant; Human; Hydrophobicity; Hydroquinones; Ions; Metals; Nitric Oxide; Other Therapy; Oxidation-Reduction; Oxygen; Oxygen Consumption; Pharmaceutical Preparations; Production; Quinones; Rate; Reaction; Reactive Oxygen Species; Reducing Agents; Role; Sampling; Solutions; Structure; Superoxides; Toxic effect; Ultrasonography; Work; aqueous; base; benzoquinone; chelation; cytotoxic; cytotoxicity; design; hydroquinone; irradiation; macromolecule; neoplastic cell; semiquinone; tumor

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.

醌类化合物是一类重要的抗肿瘤药物，在治疗人类疾病中有重要的应用。共同 这些化合物的特征是它们易于在化学或酶促反应中被还原， 生物介质以产生活性中间体和产物。虽然已经做出了努力， 将这些化合物的氧化还原电位与细胞毒性相关联，关于这些化合物的氧化还原电位如何与细胞毒性相关联知之甚少。 环境影响这些化合物的反应性中间体或产物的产生程度， 存在生物相关还原剂。我们的主要目的是了解相互关联的作用， 这些化合物及其中间体，半醌，在测定环境和结构， 活性氧和一氧化氮中间产物的产生程度。通过了解这一点， 的细胞毒性作用，这些可以获得和设计更有效的药物基于这些类型 化合物可以开发。由于半醌稳定化增加了氧消耗速率 在还原剂存在下，我们现在将研究金属螯合对邻半醌的影响。 稳定性和氧消耗。与往年相比，自最受认可的 决定肿瘤细胞形成和死亡的重要大分子是DNA分子， 现在已经将我们的注意力转移到DNA损伤反应中的阳离子，中性和阴离子醌， 还原剂的存在和不存在，以及氧的存在和不存在。醌是 已知被还原为单电子中间体半醌，随后产生 电子转移到氧气后的活性氧自由基。此外，半醌类化合物还能降低硝酸盐的含量， 氧化物转化为亚硝酰基离子，从而导致该物种的毒性。