Exploring the N-terminus region: synthesis, bioactivity and 3D-QSAR of allatostatin analogs as novel insect growth regulators
Exploring the N-terminus region: synthesis, bioactivity and 3D-QSAR of allatostatin analogs as novel insect growth regulators
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探索 N 末端区域：作为新型昆虫生长调节剂的 Allatostatin 类似物的合成、生物活性和 3D-QSAR
DOI：
10.1016/j.cclet.2017.11.022
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发表时间：
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影响因子：
9.1
通讯作者：
Xinling Yang
中科院分区：
文献类型：
--
作者：
Meizi Wang;Li Zhang;Xianwei Wang;Yun Ling;Xiaoqing Wu;Xinlu Li;Yiduo Mi;Xinling Yang
Allatostatins (ASTs), a family of insect neuropeptide, can inhibit juvenile hormone (JH) biosynthesis by the corpora allata (CA) inDiploptera punctata, and therefore be regarded as potential leads for the discovery of new insect growth regulators (IGRs). But several shortcomings, such as their sensitivity to peptidases and high cost, impeded their practical application in pest management. In order to discover new IGRs, one AST analogB1possessing non-peptide group was discovered with high ability to inhibit JH biosynthesisin vitro(IC50: 0.09 μmol/L) in our previous studies. In the present work, two series ofB1analogs with different substituents on theN-terminus region were designed and synthesized. The result suggested that benzene showed better activity than other heterocycles, and thepara-substitution on the benzene was beneficial for activity. Moreover, analogs with logPvalue over 2.0 exhibited good activity, which indicated the hydrophobicity is important to the bioactivity. Three dimension quantitative structure-activity relationship (3D-QSAR) studies were performed to highlight the structural requirements of AST analogs, which demonstrated introduction of bulkier substituents on theN-terminus would increase the activity. AnalogII12(IC50: 0.08 μmol/L) exhibited similar inhibitory activity to the leadB1, but its synthetic route was simpler thanB1. Therefore,II12could be used as a new lead compound for the discovery eco-friendly IGRs.
