Bioassay-Guided Isolation and Structural Modification of the Anti-TB Resorcinols from Ardisia gigantifolia
Bioassay-Guided Isolation and Structural Modification of the Anti-TB Resorcinols from Ardisia gigantifolia
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生物测定引导下巨叶紫金牛中抗结核间苯二酚的分离和结构修饰
DOI：
10.1111/cbdd.12756
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发表时间：
2016-08-01
影响因子：
3
通讯作者：
Zhang, Hong-Jie
中科院分区：
文献类型：
--
作者：
Guan, Yi-Fu;Song, Xun;Zhang, Hong-Jie
结核病（TB）是一种高度接触性传染病，主要由结核分枝杆菌（Mycobacterium tuberculosis）H37 RV引起。对药用植物紫金牛的叶和茎的CHCl 3提取物进行抗结核（抗TB）生物测定引导的分离，导致分离出两种抗TB 5-烷基间苯二酚，5-（8 Z-十七烯基）间苯二酚（1）和5-（8 Z-十五烯基）间苯二酚（2）。基于这两种天然产物，我们进一步合成了15个衍生物。评价这些化合物（天然的和合成的）对结核分枝杆菌H37 RV的抗TB活性。间苯二酚1和2表现出抗TB活性，在MABA测定中MIC值分别为34.4和79.2 μ M，在LORA测定中MIC值分别为91.7和168.3 μ M。在这些衍生物中，发现化合物8比其合成前体（2）显示出改善的抗TB活性，在MABA测定中MIC值为42.0 μ M，在LORA测定中为100.2 μ M。这些活性化合物作为一类新型抗结核药物值得进一步研究。基于这些衍生物，阐明了母体化合物独特的构效关系。
Tuberculosis (TB) is a highly contagious disease mainly caused by Mycobacterium tuberculosis H37RV. Antitubercular (anti-TB) bioassay-guided isolation of the CHCl3 extract of the leaves and stems of the medicinal plant Ardisia gigantifolia led to the isolation of two anti-TB 5-alkylresorcinols, 5-(8Z-heptadecenyl) resorcinol (1) and 5-(8Z-pentadecenyl) resorcinol (2). We further synthesized 15 derivatives based on these two natural products. These compounds (natural and synthetic) were evaluated for their anti-TB activity against Mycobacterium tuberculosis H37RV. Resorcinols 1 and 2 exhibited anti-TB activity with MIC values at 34.4 and 79.2 mu M in MABA assay, respectively, and 91.7 and 168.3 mu M in LORA assay, respectively. Among these derivatives, compound 8 was found to show improved anti-TB activity than its synthetic precursor (2) with MIC values at 42.0 mu M in MABA assay and 100.2 mu M in LORA assay. The active compounds should be regarded as new hits for further study as a novel class of anti-TB agents. The distinct structure-activity correlations of the parent compound were elucidated based on these derivatives.