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条件下还原相应母体化合物后与DNA共价结合。 已经发现这种行为在实体瘤的治疗中是有价值的。 如果这些醌类和硝基芳香族化合物可以通过超声诱导的空化作用减少，则应该实现更好的肿瘤/正常细胞选择性比，因为超声照射可以被引导到所选择的组织。 因此，该AREA申请的一般目的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超声分解被一个或多个电子还原。 第二个主要目的是确定在含有DNA和这些生物还原性化合物的溶液的超声辐照期间DNA是否被烷基化。 与DNA的共价结合将在UPR医学科学校区检测到，这将开启UPRH和UPR医学科学校区之间的合作。 本科生将参加这个项目，从而提高他们的资格，追求生物医学研究事业。