OXIDATION CHEMISTRY OF INDOLES

吲哚的氧化化学

• 批准号: 3281130
• 负责人: GLENN DRYHURST
• 金额: $ 11.36万
• 依托单位: UNIVERSITY OF OKLAHOMA
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-09-15 至 1991-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3281130
• 关键词: 5 hydroxytryptophan; electrochemistry; indoles; neurotoxins; neurotransmitters; oxidation; quinones; serotonin; tryptophan

The aim of this project is to employ electrochemical and other analytical techniques to investigate the oxidation chemistry of naturally occurring or otherwise biologically significant indoles. These will include the 5-hydrosylated metabolites of tryptophan, N-methylated indoles (such as bufotenin) which are implicated in the etiology of schizophrenia and depression, and 5,6- and 5,7-dihydrosytryptamines (5,6- and 5,7-DHT) which are powerful neurotoxins. Anomalous, minor oxidation pathways of, for example, the enurotransmitter 5-hydrosytryptamine have been speculated to play a role in some mental disorders. Similarly, the neurotoxicity of 5,6- and 5,7DHT is thought to be due to reactions of their reactive autoxidation products in the CNA. Many of these indoles undergo oxidation reactions in biological systems yet virtually nothing is known about the mechanisms and products of these processes. Modern electroanalytical techniques will be used to elucidate the nature of the primary oxidation step and the identity and properties of transient intermediates. Longer lived intermediates will be further studied using spectral and chromatographic methods, particularly GC-MS and LC-MS techniques. Reaction products will be isolated and identified using a wide range of analytical techniques including column chromatography, HPLC, U.V.-vis, I.R., NMR and mass spectrometry. Evidence concerning the biological relevance of such studies will be obtained by investigating the oxidation of these indoles with various CNS enzymes and critically comparing the courses of the electrochemical and enzymatic oxidations. In vivo evaluations of the neurotoxic properties of the many new products formed by electrochemical and enzymatic oxidation are planned. Electrochemical and other analytical techniques will be used to study the interactions of the very reactive primary oxidation products of indoles (quinones, quinoneimines, methyleneimines) with nucleophiles commonly found in CNS tissue (thiols, amino acids, water). The long range goal is to develop a fundamental understanding of the oxidation chemistry of biologically significant indoles. This, in turn, could provide a basis for understanding the oxidation chemistry of such indoles in living systems which might give important insights into a chemical basis for some mental illnesses and other disease states.

该项目的目的是利用电化学和其他分析方法， 研究天然存在或 否则具有生物学意义的吲哚。 这些机制将包括 5-色氨酸的水解代谢物、N-甲基化吲哚（如 蟾毒内酯），其与精神分裂症的病因学有关， 抑郁症和5，6-和5，7-二氢色胺（5，6-和5，7-DHT）， 是强大的神经毒素 不正常的，轻微的氧化途径， 例如，推测神经递质5-羟色胺 在某些精神疾病中发挥作用。 同样，5，6- 和5，7 DHT被认为是由于它们的反应性自氧化反应 产品在CNA 其中许多吲哚会发生氧化反应， 生物系统，但几乎没有什么是已知的机制， 这些过程的产物。 现代电分析技术将是 用于阐明初级氧化步骤的性质和鉴别 和瞬态中间体的性质。 寿命更长的中间体将 使用光谱和色谱方法进行进一步研究，特别是 GC-MS和LC-MS技术。 反应产物将被分离， 使用广泛的分析技术，包括色谱柱， 色谱法、HPLC、U. V. -维斯，I.R.，NMR和质谱。 证据 关于这些研究的生物学相关性，将通过以下方式获得 研究这些吲哚与各种CNS酶的氧化， 对电化学和酶促反应过程进行了批判性的比较， 氧化 许多神经毒性特性的体内评价 通过电化学和酶促氧化形成的新产物， 计划好了 电化学和其他分析技术将用于 研究非常活跃的初级氧化产物的相互作用， 吲哚（醌、醌亚胺、亚甲基亚胺）与亲核试剂 常见于CNS组织（硫醇、氨基酸、水）。 远程 目标是对氧化化学有基本的了解 具有生物学意义的吲哚。 这反过来又可以提供一个基础 为了理解生命系统中吲哚的氧化化学， 这可能会给我们一些重要的启示， 疾病和其他疾病。