Synthesis, aphicidal activity and conformation of novel insect kinin analogues as potential eco-friendly insecticides.
Synthesis, aphicidal activity and conformation of novel insect kinin analogues as potential eco-friendly insecticides.
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DOI：
10.1002/ps.5721
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发表时间：
2019-12
影响因子：
4.1
通讯作者：
Chuanliang Zhang;Xinlu Li;D. Song;Yun Ling;Yuan-Lin Zhou;Xinling Yang
中科院分区：
文献类型：
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作者：
Chuanliang Zhang;Xinlu Li;D. Song;Yun Ling;Yuan-Lin Zhou;Xinling Yang
背景由于传统杀虫剂对蜜蜂产生了很大的抗药性和意想不到的生态毒性，通过新的蚜虫控制策略发现生态友好的杀虫剂非常重要。昆虫激肽是一类多功能的昆虫神经肽，在害虫防治中具有潜在的应用价值。在前期的工作中，我们开发了几个系列的昆虫激肽类似物，并发现了一个具有良好杀蚜活性的先导化合物II-1。为了进一步发现生态友好型杀蚜剂，本文对II-1进行了进一步的优化。结果合成了15个新的Yaa 3修饰的II-1先导化合物。杀蚜试验结果表明，IV-3、IV-5和IV-10对大豆蚜（Aphis glycines）具有明显的活性，LC_（50）分别为0.0029、0.0072和0.0086 mmol/L，高于铅II-1和吡蚜酮。分子模拟结果表明，类似物II-1、IV-3、IV-5、IV-7和IV-10形成了β-转角样构象，而类似物IV-1、IV-2和IV-9的构象似乎是线性的。通过对类似物构效关系的分析，提出了有利于活性的结构单元。结论以Ⅱ-1为先导化合物，在Yaa 3水解位点上引入天然的、位阻的α-和β-氨基酸，合成的昆虫激肽类化合物在开发环境友好型杀虫剂方面具有重要的应用前景。令人鼓舞的是，最活跃的类似物IV-3可以成为进一步开发的候选者。Phe 2和Trp 4侧链的β-转角构象和芳香环的取向可能是影响活性的关键因素。本文受版权保护。All rights reserved.
BACKGROUND The discovery of ecofriendly insecticides through new strategy for aphid control is important because of the substantial resistance and unexpected eco-toxicity to honeybees caused by traditional insecticide. The insect kinins, a class of multifunctional insect neuropeptides, are considered for potential application in pest control. In our previous work, we have developed several series of insect kinin analogues and found a promising lead II-1 with good aphicidal activity. For the further discovery of eco-friendly aphicides, the further optimization on II-1 is carried out herein. RESULTS 15 novel Yaa3 modified analogues based on the lead II-1 were synthesized. The aphicidal tests indicated that IV-3, IV-5, and IV-10 exhibited significant activity against the soybean aphid Aphis glycines with LC50 values of 0.0029, 0.0072 and 0.0086 mmol/L, respectively, higher than that of lead II-1 and the commercial Pymetrozine. The molecular modeling results showed that analogues II-1, IV-3, IV-5, IV-7 and IV-10 formed a β-turn-like conformation, while the conformation of analogues IV-1, IV-2 and IV-9 seemed to be linear. Some structural elements favorable for the activity were proposed based on the analysis of analogues conformation-activity relationship. CONCLUSION Insect kinins analogues derived from lead II-1 by modifying the hydrolysis site Yaa3 with natural, sterically hindered α- and β-amino acids showed great potency in the discovery of eco-friendly insecticides. Inspiringly, the most active analogue IV-3 can be a candidate for further development. The β-turn-like conformation and the orientation of the aromatic rings of the side chain of Phe2 and Trp4 may be critical factors beneficial to activity. This article is protected by copyright. All rights reserved.