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Metabolism of N-Containing Polycyclic Aromatic Hydrocarbons

含氮多环芳烃的代谢

基本信息

批准号：
63044120
负责人：
KAWAZOE Yutaka
金额：
$ 3.07万
依托单位：
Nagoya City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1990
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-63044120/
关键词：
quinoline nitrogen-containing aromatics lignin metabolism mutagenicity genotoxicity carcinogenicity AIDS

项目摘要

This research aimed at establishment of the metabolic process involved in the activation of genotoxic N-containing polycylic aromatic hydrocarbons. The bay-region theory was proposed by Jerina, one of the counterparts of this joint research, on the activation of polycyclic aromatic hydrocarbons, but no systematic study hasnot yet been achieved on the activation of those containing hetero atom(s) such nitrogen and oxygen in the aromatic system. We have revealed that the activated form of quinoline may be the 2, 3-oxide of quinoline 1, 4-hydrate, which is a new type of activated epoxide different from the bay-region epoxides proposed to polycyclic aromatic hydrocarbons. This working hypothesis has been further evidenced by the matabolism of halogno- and methyl-substituted quinoline derivatives. Based on this activation methanism, we proposed that, when fluorine is substituted on the position-3 of the quinoline ring, those derivatives would be completely deprived of genotoxicity. This proposal has been experimentally proven with several examples.In the latter part of this 3-year joint research, we have extended the study to the bioactive lignin-related compounds, which are the oxygen-containing polymeric aromatic compounds. We found that several natural and synthetic lignins had diverse biological activities including antiviral and antimicrobial activity, and in addition, immunopotenting activity. Lignin skeletal structure is essentially required for the antiviral activity, whereas some hemicellulose appendages attached to the lignin skeleton are also required for immunopotentiating activity leading to antimicrobial activity. This research strongly suggests that more attention should be paid to the lignified materials, both natural and synthetic, as a potential medicinal resource.

本研究旨在建立参与活化遗传毒性的含氮多环芳烃的代谢过程。多环芳烃的活化是由合作研究对象之一Jerina提出的海湾区理论，但对芳烃体系中含氮、氧等杂原子的多环芳烃的活化还没有系统的研究。我们发现喹啉的活化形式可能是喹啉1，4-水合物的2，3-氧化物，它是一种不同于多环芳烃的湾区环氧化物的新型活化环氧化物。这一工作假设已进一步证明了卤代和甲基取代的喹啉衍生物的matenance。基于这一活化机理，我们提出，当喹啉环的3位上被氟取代时，这些衍生物将完全丧失遗传毒性。这一提议已经通过几个例子得到了实验证明。在这3年的联合研究的后期，我们将研究扩展到了具有生物活性的木质素相关化合物，即含氧高分子芳香族化合物。我们发现，几种天然和合成的木质素具有不同的生物活性，包括抗病毒和抗菌活性，此外，免疫增强活性。木质素骨架结构是抗病毒活性所必需的，而连接到木质素骨架上的一些半纤维素附属物也是导致抗微生物活性的免疫增强活性所必需的。这一研究强烈表明，应更多地关注天然和合成的木质素材料，作为一种潜在的药用资源。