Reduction of Alkylating Quinones and Nitroarenes

烷基化醌和硝基芳烃的还原

• 批准号: 6656764
• 负责人: ANTONIO E ALEGRIA
• 金额: $ 13.9万
• 依托单位: UNIVERSITY OF PUERTO RICO AT HUMACAO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6656764
• 关键词: DNA damage; NAD(P)H dehydrogenase; adduct; alkylation; biochemistry; chemical reaction; covalent bond; electron spin resonance spectroscopy; gas chromatography mass spectrometry; hypoxia; neoplasm /cancer therapy; nitro compounds; nuclear magnetic resonance spectroscopy; oxygen; quinones; reduction

DESCRIPTION (provided by applicant): Intermediates of bioreductive alkylating quinones and nitroarenes are known to bind covalently to DNA after reduction of the corresponding parent compound under hypoxia. Such a behavior has been found to be valuable in the treatment of solid tumors. Better tumor/normal cell selectivity ratio should be achieved if these quinones and nitroaromatics could be reduced through ultrasound-induced cavitation since ultrasound irradiation can be directed to the selected tissue. Thus, one of the general aims of this AREA application is to determine if alkylating quinones and nitroaromatics are reduced by one or more electrons through the sonolyses of these quinones and nitroarenes. A second major aim is to determine if DNA is alkylated during ultrasound irradiation of solutions containing DNA and these bioreductive compounds. Covalent binding to DNA will be detected at UPR-Medical Sciences campus, which will open collaboration between faculty of UPRH and UPR-Medical Sciences Campus. Undergraduate students will participate in this project, thus improving their qualifications to pursue biomedical research careers.

描述（由申请人提供）：已知生物还原性烷基化醌和硝基芳烃的中间体在缺氧下还原相应的母体化合物后与DNA共价结合。 已发现这种行为在实体瘤的治疗中很有价值。 如果这些醌和硝基芳香族化合物可以通过超声诱导的空化作用来减少，则应该实现更好的肿瘤/正常细胞选择性比，因为超声辐射可以定向到选定的组织。 因此，该 AREA 应用的总体目标之一是确定烷基化醌和硝基芳烃是否通过这些醌和硝基芳烃的声解被一个或多个电子还原。 第二个主要目标是确定在超声波照射含有 DNA 和这些生物还原性化合物的溶液期间 DNA 是否被烷基化。 与 DNA 的共价结合将在 UPR 医学科学校区进行检测，这将开启 UPRH 教师和 UPR 医学科学校区之间的合作。 本科生将参与该项目，从而提高他们从事生物医学研究职业的资格。