青蒿素及其衍生物的抗疟构效关系研究和治疗新适应症衍生物的发现

发布时间：2018-04-27 15:12

本文选题：青蒿素 + 抗疟药物　；参考：《科学通报》2017年18期

【摘要】：青蒿素及其衍生物蒿甲醚、青蒿琥酯在抗疟领域取得了巨大成功,尤其对脑型疟疾和抗氯喹耐药表现出很好的疗效.本文首先对青蒿素及其衍生物的构效关系进行了回顾,系统分析了采用量子化学计算、三维定量构效关系分析、还原电势检测,以及分子对接等不同手段对于研究青蒿素衍生物结构优化,阐明其潜在作用机制方面的指导作用.除了抗疟作用,青蒿素及其衍生物还具有显著的免疫调节功能.近年来,通过对青蒿素类化合物开展了以免疫调节活性为导向的药物化学与药理学相结合的系统研究,在青蒿素母体结构上引入新的基团,发现了一批具有更强免疫抑制活性以及口服吸收良好的新型青蒿素衍生物.其次,主要介绍这些新型青蒿素类衍生物在治疗自身免疫疾病方面的研究进展.为了充分挖掘青蒿素骨架在药物研发方面的潜力,从20世纪90年代开始有越来越多的研究开始探索青蒿素及其衍生物的抗肿瘤活性.青蒿素本身或其简单的衍生物,如双氢青蒿素、蒿甲醚、蒿乙醚等的抗肿瘤活性较弱.然而,通过采用向青蒿素骨架中引入水溶性片段、杂多环,以及靶向药物片段等策略,可以获得抗肿瘤活性更好,成药性更高,且具有明确分子靶标的新型青蒿素衍生物.最后,对新型抗肿瘤青蒿素衍生物的设计和改造最新进展进行了综述.
[Abstract]:Artemisinin and its derivatives artemether artesunate and artesunate have achieved great success in the field of antimalarial especially in the treatment of cerebral malaria and chloroquine resistance. In this paper, the structure-activity relationships of artemisinin and its derivatives are reviewed, and the quantum chemical calculation, three-dimensional quantitative structure-activity relationship analysis and reduction potential detection are systematically analyzed. Different methods such as molecular docking can be used to optimize the structure of artemisinin derivatives and clarify their potential mechanism. In addition to antimalarial action, artemisinin and its derivatives also have significant immunomodulatory function. In recent years, a systematic study on the combination of pharmacology and pharmacology of artemisinin compounds was carried out, and a new group was introduced into the matrix structure of artemisinin. Some new artemisinin derivatives with stronger immunosuppressive activity and good oral absorption were found. Secondly, the research progress of these new artemisinin derivatives in the treatment of autoimmune diseases is introduced. In order to fully exploit the potential of artemisinin skeleton in drug research and development, more and more researches began to explore the antitumor activity of artemisinin and its derivatives in 1990s. Artemisinin itself or its simple derivatives, such as dihydroartemisinin, artemisinin, artemisinin, artemisinin, and so on, have weak antitumor activities. However, new artemisinin derivatives with better antitumor activity, higher drug formation and clear molecular targets can be obtained by introducing water-soluble fragments, heteropolyclic rings and targeted drug fragments into artemisinin skeleton. Finally, the design and modification of new anti-tumor artemisinin derivatives are reviewed.
【作者单位】：中国科学院上海药物研究所;上海科技大学生命科学与技术学院;
【分类号】：R978.6

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