青黛中靛红的结构改造及体外抗菌活性研究

发布时间：2019-04-02 21:10

【摘要】：目的：分离青黛中有效成分靛红(ISA, isatin),对其进行结构改造得到一系列全新化合物,进行活性研究,为研发具有自主知识产权的靛红类新药打下基础。方法：1.用经典的水蒸气蒸馏法和层析分离方法从中药青黛中分离ISA；2.运用国际前沿的有机合成方法,以ISA为骨架出发合成一系列全新的具有多个手性中心的3位吲哚氧杂螺环化合物并用1HNMR、13CNMR、HRMS进行结构鉴定：3.采用琼脂平板二倍稀释法测定底物、目标化合物及其衍生物对供试菌的最小抑菌浓度。结果：1.青黛中ISA分离结果：得到纯度高于90%的橙红色晶体,与ISA标准品进行薄层层析对比得到相同的Rf值；2.结构改造结果：实验过程中共合成22个化合物,包括16个均未见报道的目的化合物,所有目的化合物的结构都经1HNMR、13CNMR、HRMS分析确证,并进行了熔点和旋光度的测定；3.对靛红N位进行苄基修饰得到的产物可略微增加靛红对某些菌种的抑制作用,而进一步改造得到的部分目标产物及其衍生物据初步研究没有明显的抗菌活性,体外抗肿瘤活性的初筛显示其中有目标产物对前列腺癌细胞LNCaP的增殖有一定的抑制作用。结论：以从青黛中分离的有效成分ISA为核心骨架的改造产物吲哚醌3位氧杂螺环化合物失去了原本的抗菌活性,推测靛红的3-位羰基可能为ISA抗菌活性的有效基团。
[Abstract]:Aim: to obtain a series of new compounds by structural modification of indirubin (ISA, isatin), which is an effective component of Qingdai, and to study its activity so as to lay a foundation for the research and development of new indigo drugs with independent intellectual property rights. Methods: 1. Separation of ISA;2. from Qingdai traditional Chinese medicine by classical steam distillation and chromatography A series of novel 3-position indole-oxo heterocyclic compounds with multiple chiral centers were synthesized by using the advanced organic synthesis method in the world, using ISA as the framework and 1HNMR, 13CNMR. the structure of the compounds was identified as follows: 3. The minimal inhibitory concentration (MIC) of substrate, target compounds and their derivatives against tested bacteria was determined by Agar plate dilution method. Results: 1. The results of ISA separation in Qingdai showed that orange-red crystal with purity higher than 90% was obtained and the same RF value was obtained by thin-layer chromatography (TLC) with ISA standard; Results of structural modification: 22 compounds were synthesized during the experiment, including 16 unreported target compounds. The structures of all compounds were confirmed by 1HNMR, 13CNMR and HRMS, and the melting point and optical rotation were determined. The product modified by benzyl group on N site of Indigo can slightly increase the inhibitory effect of indirubin on some strains, but some of the target products and their derivatives obtained by further modification have no obvious antibacterial activity according to the preliminary study. The primary screening of anti-tumor activity in vitro showed that the target product could inhibit the proliferation of prostate cancer cell line LNCaP to a certain extent. Conclusion: the modified product of indolequinone-3-oxo-helicyclic compound with the core skeleton of ISA isolated from Qingdai has lost its original antibacterial activity. It is suggested that the 3-carbonyl group of indirubin may be the effective group of the antibacterial activity of ISA.
【学位授予单位】：成都中医药大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R285

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