Marine Fatty Acids as New Antifungal, Antimycobacterial, and Topo-l Agents

海洋脂肪酸作为新型抗真菌、抗分枝杆菌和拓扑醇药物

• 批准号: 7491954
• 负责人: Nestor Manuel Carballeira
• 金额: $ 21.92万
• 依托单位: UNIVERSITY OF PUERTO RICO RIO PIEDRAS
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7491954
• 关键词: Acids; Acyl Carrier Protein; Affect; Animal Feed; Antifungal Agents; Antimycobacterial Agents; Binding; Biochemistry; Biogenesis; Biological; Biological Assay; Biota; Cells; Characteristics; Chemistry; Cholesterol; Classification; Collaborations; Communicable Diseases; Complex; Cyclopropanes; Data; Dementia; Development; Diet; Diffuse; Disease; Drug Formulations; Environment; Enzymes; Escherichia coli; Eukaryota; Eukaryotic Cell; Evaluation; Fatty Acids; Food; Food Additives; Genus Mycobacterium; Goals; Hand; Health; High Density Lipoprotein Cholesterol; Human; Journals; Knowledge; LDL Cholesterol Lipoproteins; Laboratories; Laboratory Research; Lipids; Literature; Malignant Neoplasms; Marines; Membrane; Mental Depression; Methods; Molds; Molecular; Mycobacterium tuberculosis; Mycoses; Mycotoxins; Myocardial Infarction; Omega-3 Fatty Acids; Organism; Oxidoreductase; Play; Positioning Attribute; Prevalence; Prevention; Property; Protocols documentation; Publishing; Range; Reporting; Research; Research Design; Risk; Role; Score; Series; Site; Structure; Structure-Activity Relationship; System; Testing; Today; Topoisomerase; Toxic effect; Trans Fatty Acids; Tuberculosis; Type I DNA Topoisomerases; Work; Yeasts; antimicrobial; base; carbene; cyclopropane; disorder control; editorial; enantiomer; enoyl reductase; expectation; experience; functional group; fungus; human TOP1 protein; infectious disease treatment; inhibitor/antagonist; innovation; marine organism; novel; prevent; success; symposium

DESCRIPTION (provided by applicant): Fatty acids play a critical role in human health. Our research group has been active in discovering new fatty acids from marine biota whose structures differ significantly from those of fatty acids normally encountered in terrestrial organisms. It is our aim to study further these novel fatty acids so as to better understand their biochemistry and their potential use in health related problems. In particular, we wish to answer the following questions: 1) Are the structural features of the novel marine fatty acids sufficiently different from those present in common fatty acids so as to significantly alter their biogenesis in prokaryotic and eukaryotic cells? 2) Will the marine fatty acids be sufficiently different from the more common and better studied fatty acids in their toxicity towards pathogenic agents such as fungi and/or mycobacteria? 3) Will the marine fatty acids be useful in helping to prevent and/or control diseases arising from fungi and mycobacteria? If the most unusual marine fatty acids are toxic to the causative agents of infectious diseases, then we can use them in food formulations and supplements that could help in the prevention, reduction, and/or treatment of fungal infections and/or more complex diseases such as tuberculosis. Our long-range goal, therefore, is to identify novel marine fatty acids with the potential of helping in the prevention, reduction, and/or treatment of infectious diseases. The objective of this application, which is the next step toward attainment of our long-range goal, is to explore the chemistry and toxicity of 2-methoxylated 5,9-diunsaturated fatty acids, mid-chain methoxylated fatty acids, and 4,5-methylene fatty acids by: (1) developing the first synthesis for racemic and quiral 2-methoxylated 5,9-diunsaturated fatty acids and determining their antimycobacterial, InhA, and topoisomerase-l inhibitory activities, (2) synthesizing a series of mid-chain methoxylated fatty acids and study their enoyl reductase (EcFabl) inhibitory activity, (3) developing the first synthesis for racemic and optically active 4,5-methylene fatty acids and determining their antifungal and antimycobacterial potential, and (4) carrying out a developmental plan to achieve competitiveness of the PI for non-SCORE support. At the end of this project we will provide new fatty acids that will be made available to biochemists, cell biologists, and pharmacologists to be used against these diseases. The novel antifungal compounds could also be used as yeast and mold inhibitors in food stuffs and as systematic antifungals.

描述（由申请人提供）：脂肪酸在人类健康中起关键作用。我们的研究小组一直积极发现来自海洋生物群的新脂肪酸，其结构与通常在陆生生物中遇到的脂肪酸的结构显着不同。我们的目的是进一步研究这些新型脂肪酸，以更好地了解它们的生物化学及其在与健康相关问题中的潜在用途。特别是，我们希望回答以下问题：1）新型海洋脂肪酸的结构特征是否与普通脂肪酸中的那些完全不同，以显着改变其在原核生物和真核细胞中的生物发生？ 2）海洋脂肪酸是否与对真菌和/或分枝杆菌等致病剂的毒性中更常见和更好地研究的脂肪酸有足够的不同？ 3）海洋脂肪酸是否有助于预防和/或控制真菌和分枝杆菌引起的疾病？如果最不寻常的海洋脂肪酸对传染病的病因有毒，那么我们可以将它们用于食物配方和补充剂中，可以帮助预防，减少和/或治疗真菌感染和/或更复杂的复杂疾病，例如结核病。因此，我们的远程目标是确定新型的海洋脂肪酸，具有帮助预防，减少和/或治疗传染病的潜力。该应用的目标是实现我们远程目标的下一步，是探索2-甲氧基化的5,9-二氧饱和脂肪酸的化学和毒性，中链甲氧基脂肪酸和4,5-甲基烯脂肪酸的中链和4,5-甲基脂肪酸，（1）通过：（1）通过：（1）对种族和quiral fatie forection和quiryal fatie forection and fatey fatie forection and fateigy 5,9.999. （2）确定它们的抗菌抗菌，INHA和拓扑异构酶-L抑制活性，（2）合成一系列中链甲氧基化的脂肪酸并研究其Enoyl还原酶（cofblabl）抑制活性，（3）开发出对甲壳虫和光学活跃的4,5-甲基元素的首次合成，并确定其静态酸性酸性和确定性酸性和确定性酸性，并确定其确定性酸性酸性和确定性含量， （4）执行开发计划，以实现PI的竞争力来实现非分数支持。在该项目结束时，我们将提供新的脂肪酸，这些脂肪酸将为生物化学家，细胞生物学家和药理学家提供，以用于这些疾病。新型的抗真菌化合物也可以用作食物食品和系统抗真菌剂中的酵母和霉菌抑制剂。