Systematic activity-oriented separation and structure-activity relationship of tobacco cembranoids

文献类型： 外文期刊

第一作者： Wang, Jiao

作者： Wang, Jiao;Xu, Kuo;Ren, Guangwei;Zhang, Zhongfeng;Du, Yongmei;Zhang, Jianhui;Yang, Xingyou;Xiao, Yong;Zhang, Yayu

作者机构：

关键词： Tobacco cembranoids; Preparative reversed-phase liquid chromatography; Systematic activity-oriented separation; Bioactivity evaluation; Structure-activity relationship

期刊名称：INDUSTRIAL CROPS AND PRODUCTS （ 影响因子：5.645； 五年影响因子：5.749 ）

ISSN： 0926-6690

年卷期： 2021 年 173 卷

页码：

收录情况： SCI

摘要： Cembranoids are a class of glandular trichome exudates with a variety of structural variations and biological activities, and are found in high quantities in tobacco (Nicotiana tabacum L.). However, few studies have conducted preparative separation and examined the activities of cembranoids other than (1S,2E,4S,6R,7E,11E)-2,7,11-cembratriene-4,6-diol (alpha-CBT-diol, 1) and (1S,2E,4R,6R,7E,11E)-2,7,11-cembratriene-4,6-diol (beta-CBT-diol, 2); thus, the structure-activity relationship (SAR) of cembranoids remains unclear. Here, to deduce the SAR of cembranoids, raw cembranoid extract was systematically separated through an activity-oriented approach with preparative reversed-phase liquid chromatography. Each fraction was identified, and their antifungal, insecticidal, and cytotoxic bioactivities were evaluated. Composition analysis and activity detection of primary fractions (Fr.1-Fr.10) revealed that cembranoid activity might be influenced by the number of hydroxyl groups and degree of unsaturation (macrocycle and double bonds). Sub-fraction analysis showed that the antifungal activity of cembranoids was related to the number of hydroxyl groups and double bonds, and that their cytotoxic activity was affected by the type and position of substituents. Furthermore, all four factors could influence insecticidal activity. By conducting in-depth studies of single cembranoids, their SARs were summarized. The existence of Delta(11,12)/Delta(7,8) and hydroxylation at C-6/C-4 contributed to the antifungal activity of cembranoids. Variation in the type and position of substituents also significantly affected antifungal activity, of which Delta(11,12) was the most influential factor. Additionally, the change in substituent configuration at C-4 and C-12 had no significant effect on antifungal activity. The insecticidal activity of cembranoids benefited from the existence of 4-hydroxyl, which greatly enhanced their binding affinity; however, functional groups substituted at other positions decreased insecticidal activity. Cytotoxic activity was positively correlated with a-configuration at C-4 and hydroxylation at C-6 but inversely correlated with 4-methoxy substitution. Among them, 6-hydroxyl formed the core; the alpha-/beta-configuration at C-12 and 4-/12-substitution of cembranoids did not affect their insecticidal activity. Insecticidal activity might play a key role by restraining acetylcholinesterase activity through hydrophobic interactions between the cembranoid carbon skeleton and residues located at the acetylcholinesterase binding pocket. These findings may provide a foundation for the development of novel cembranoid-based pesticides and medicines.

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