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天然马兜铃酸生物碱马兜铃内酰胺-β-D-葡萄糖苷:与生物大分子的相互作用及与生物学观点的相关性。

Natural Aristolochia Alkaloid Aristololactam-β-D-glucoside: Interaction with Biomacromolecules and Correlation to the Biological Perspectives.

机构信息

Biophysical Chemistry Laboratory, Organic and Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India.

出版信息

Mini Rev Med Chem. 2018;18(12):1022-1034. doi: 10.2174/1389557518666180222170050.

Abstract

BACKGROUND

Natural aristolochia alkaloids have attracted the attention of both chemists and biologists from the stand point of their structural and pharmacological aspects. Many of the compounds isolated in this group are potent tumor inhibitors. These are divided into nitrophenanthrinic acid, phenanthrene lactams and isoquinoline alkaloids. A number of structure-activity studies have been performed on aristolochia alkaloids. Of particular interest is the molecule with the β-D-glucoside moiety that has similarity to the clinical anticancer agent daunomycin.

OBJECTIVE

The anticancer activity of aristololactam-β-D-glucoside has been thought to be due to its DNA and RNA binding activities among other actions. In this article we focus on the physicochemical property of this alkaloid and the structural and functional aspects of its binding to different nucleic acid and protein structures.

METHODS

This review highlights a large number of biophysical studies employing various analytical techniques like absorbance, fluorescence, circular dichroism, thermal melting, viscosity, IR study, isothermal calorimetry and differential scanning calorimetry.

RESULT

The detailed binding mechanism in terms of the structural and thermodynamic aspects at the molecular level has been discussed.

CONCLUSION

This review enables to assess the high potential of developing aristololactam-β-Dglucoside and related alkaloids as therapeutic agents.

摘要

背景

天然马兜铃生物碱因其结构和药理方面的特点,引起了化学家及生物学家的关注。从该类物质中分离得到的许多化合物都具有很强的抗肿瘤活性。它们可分为硝基菲类酸、菲类内酰胺和异喹啉生物碱。人们对马兜铃生物碱进行了大量的构效关系研究。其中特别引人注目的是具有β-D-葡萄糖苷部分的分子,它与临床抗癌药物道诺霉素相似。

目的

马兜铃内酰胺-β-D-葡萄糖苷的抗肿瘤活性被认为与其 DNA 和 RNA 结合活性等有关。本文重点介绍了该生物碱的物理化学性质,以及其与不同核酸和蛋白质结构结合的结构和功能方面。

方法

本文综述了大量的生物物理研究,采用了各种分析技术,如吸收、荧光、圆二色性、热融解、粘度、IR 研究、等热滴定法和差示扫描量热法。

结果

讨论了在分子水平上的结构和热力学方面的详细结合机制。

结论

本文的综述使人们能够评估开发马兜铃内酰胺-β-D-葡萄糖苷和相关生物碱作为治疗剂的巨大潜力。

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