Synthesis of atypical carotenoids: self-preserving inhibitors of lipid peroxidati

非典型类胡萝卜素的合成：脂质过氧化物的自我保护抑制剂

基本信息

批准号：
7993589
负责人：
Martin D Burke
金额：
$ 29.74万
依托单位：
UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-12-01 至 2013-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7993589
关键词：
Address Age related macular degeneration Antioxidants Arthritis Asthma Atherosclerosis Attenuated Biochemical Biological Factors Carotene Carotenoids Cell membrane Cells Chemicals Clinical Clinical Trials Collection Combinatorial Synthesis Communities Complex Conduct Clinical Trials Coupling Development Diabetes Mellitus Disease Employee Strikes Foundations Functional disorder Future Generations Goals Health Human In Vitro Investigation Knowledge Lead Letters Lipid Bilayers Lipid Peroxidation Lipids Liposomes Lutein Macular degeneration Malignant Neoplasms Malignant neoplasm of lung Membrane Membrane Lipids Methods Modification Neurodegenerative Disorders Oxygen Phospholipids Plants Polyenes Preparation Principal Investigator Process Property Publications Reactive Oxygen Species Reperfusion Injury Research Rheumatoid Arthritis Role Route Safety Screening procedure Series Structure Structure-Activity Relationship Testing Therapeutic Agents Time Veins analog astaxanthine base combinatorial chemistry design flexibility heart disease prevention high throughput screening human disease improved in vivo inhibitor/antagonist interest lipid peroxidation inhibitor microorganism novel novel therapeutics oxidative damage peroxidation pre-clinical programs protective effect small molecule zeaxanthin

项目摘要

DESCRIPTION (provided by applicant): Project Summary Synthesis of atypical carotenoids: self-preserving inhibitors of lipid peroxidation Small molecules that safely and effectively inhibit the peroxidation of lipid bilayers stand to substantially advance the treatment of many prevalent human diseases, including atherosclerosis, cancer, macular degeneration, and arthritis. However, most of the known O antilipoperoxidants have important limitations. Me Me O Me H HO Me For example, typical carotenoids such as O astaxanthin have a strong propensity for self- Me HO Me peridinin (1) Me OAc destructive interactions with reactive oxygen Me species, which limits the lifetime of the lipid O protective effect and leads to the generation of HO Me Me harmful carotenoid breakdown products. In contrast, there are several recently discovered Me Me Me Me OH "atypical" carotenoids that have the potential Me for exceptional antilipoperoxidant activities via Me O synechoxanthin (2) self-preserving mechanisms of action. Specifically, this research program will develop O highly efficient and flexible syntheses of the HO O O O Me atypical carotenoids peridinin (1), HO O Me synechoxanthin (2), and di-[(6-O-oleoyl-2-D- HO Me Me Me Me glucopyranosyl)oxy]-astaxanthin (3), execute Me Me Me Me systematic structure/function studies to Me O O OO OH understand their unique antilipoperoxidant OH profiles, and extensively optimize their Me O OH activities via iterative cycles of rationally- guided combinatorial synthesis and high- di-[(6-O-oleoyl-!-D-glucopyranosyl)oxy]-astaxanthin (3) throughput screening. PHS 398/2590 (Rev. 05/01) Page Continuation Format Page PUBLIC HEALTH RELEVANCE: Project Narrative Synthesis of atypical carotenoids: self-preserving inhibitors of lipid peroxidation Several recently discovered natural products have the potential to serve as powerful antioxidants inside cell membranes, and therefore may lead to improved treatments for a variety of prevalent diseases, including atherosclerosis, cancer, and arthritis. In contrast to related antioxidants that have been studied previously, these new compounds do not self-destruct as they protect the membrane from oxidative damage, which is critical for maximizing efficacy and safety. This research program will lead to the efficient synthesis, detailed study, and extensive optimization of these novel "self-preserving" antioxidants. PHS 398/2590 (Rev. 05/01) Page Continuation Format Page

描述（由申请人提供）：非典型类胡萝卜素的项目摘要：脂质过氧化的抑制剂小分子，这些分子安全有效地抑制了脂质双层的过氧化，以实质上促进许多普遍的人类疾病的治疗方法，包括动脉粥样硬化，癌症，麦粒肿，脂肪，脂肪，脂肪，脂肪，脂肪，脂肪。但是，大多数已知的O抗氧化剂剂具有重要的局限性。例如，我的我是我，例如，典型的类胡萝卜素（例如o astaxanthin）具有强烈的自我倾向，我会与无活性氧ME物种进行OAC的破坏性相互作用，从而限制了脂质O保护效应的生命，并导致了我有害的Carotenoid崩溃的产物。相比之下，最近有几个发现我我的我哦，“非典型”类胡萝卜素，使我有潜力通过我o synechoxanthin（2）自我证明的作用机制。 Specifically, this research program will develop O highly efficient and flexible syntheses of the HO O O O Me atypical carotenoids peridinin (1), HO O Me synechoxanthin (2), and di-[(6-O-oleoyl-2-D- HO Me Me Me Me glucopyranosyl)oxy]-astaxanthin (3), execute Me Me Me Me systematic structure/function studies to Me O O OO OH understand their独特的抗膜过氧剂OH轮廓，并通过理性指导的组合合成和高di- [（6-o-oleoyl - ！ - d- d-葡萄糖基）氧气的迭代循环广泛优化其ME O OH活动。 PHS 398/2590（修订版05/01）页面延续格式页面公共卫生相关性：非典型类胡萝卜素的项目叙事综合：脂质过氧化的自我保护抑制剂最近发现的几种天然产物有可能用作细胞膜内部强大的抗氧化剂，因此可能会改善治疗各种普遍的疾病，包括各种疾病，包括障碍性疾病，包括动脉粥样硬化，癌症，癌症，癌症，癌症，癌症。与之前已经研究过的相关抗氧化剂相反，这些新化合物不会自我毁灭，因为它们保护膜免受氧化损伤，这对于最大化功效和安全性至关重要。该研究计划将导致这些新型“自我保护”抗氧化剂的有效合成，详细研究和广泛的优化。 PHS 398/2590（修订版05/01）页面延续格式页面