Synthesis and Quantitative Structure鈥揂ctivity Relationship (QSAR) Study of Novel 4-Acyloxypodophyllotoxin Derivatives Modified in the A and C Rings as Insecticidal Agents

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• 作者：Shuzhen He ; Yonghua Shao ; Lingling Fan ; Zhiping Che ; Hui Xu ; Xiaoyan Zhi ; Juanjuan Wang ; Xiaojun Yao ; Huan Qu
• 刊名：Journal of Agricultural and Food Chemistry
• 出版年：2013
• 出版时间：January 23, 2013
• 年：2013
• 卷：61
• 期：3
• 页码：618-625
• 全文大小：373K
• 年卷期：v.61,no.3(January 23, 2013)
• ISSN：1520-5118

文摘

In continuation of our program aimed at the discovery and development of natural-product-based insecticidal agents, we have synthesized three series of novel 4-acyloxy compounds derived from podophyllotoxin modified in the A and C rings, which is isolated as the main secondary metabolite from the roots and rhizomes of Podophyllum hexandrum. Their insecticidal activity was preliminarily evaluated against the pre-third-instar larvae of Mythimna separata in vivo. Compound 9g displayed the best promising insecticidal activity. It revealed that cleavage of the 6,7-methylenedioxy group of podophyllotoxin will lead to a less active compound and that the C-4 position of podophyllotoxin was the important modification location. A quantitative structure鈥揳ctivity relationship (QSAR) model was developed by genetic algorithm combined with multiple linear regression (GA-MLR). For this model, the squared correlation coefficient (R²) is 0.914, the leave-one-out cross-validation correlation coefficient (Q²_LOO) is 0.881, and the root-mean-square error (RMSE) is 0.024. Five descriptors, BEHm2, Mor14v, Wap, G1v, and RDF020e, are likely to influence the biological activity of these compounds. Among them, two important ones are BEHm2 and Mor14v. This study will pave the way for further design, structural modification, and development of podophyllotoxin derivatives as insecticidal agents.

Keywords:

podophyllotoxin; acyloxy; A and C ring modification; botanical insecticide; insecticidal activity; QSAR; Mythimna separata Walker