Bioassay-Guided Isolation and Structural Modification of the Anti-TB Resorcinols from Ardisia gigantifolia

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• 作者：Yi-Fu Guan ; Xun Song ; Ming-Hua Qiu ; Shi-Hong Luo ; Bao-Jie Wang ; Nguyen Van Hung ; Nguyen M. Cuong ; Djaja Doel Soejarto ; Harry H.S. Fong ; Scott G. Franzblau ; Sheng-Hong Li ; Zhen-Dan He and Hong-Jie Zhang
• 刊名：Chemical Biology & Drug Design
• 出版年：2016
• 出版时间：August 2016
• 年：2016
• 卷：88
• 期：2
• 页码：293-301
• 全文大小：611K
• ISSN：1747-0285

文摘

Tuberculosis (TB) is a highly contagious disease mainly caused by Mycobacterium tuberculosis H₃₇R_V. 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 H₃₇R_V. Resorcinols 1 and 2 exhibited anti-TB activity with MIC values at 34.4 and 79.2 μm in MABA assay, respectively, and 91.7 and 168.3 μm 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 μm in MABA assay and 100.2 μm 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.