Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, China.
School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418, China.
Bioorg Med Chem Lett. 2019 Apr 1;29(7):890-895. doi: 10.1016/j.bmcl.2019.02.001. Epub 2019 Feb 2.
Allatostatins (AST) are neuropeptides originally described as inhibitors of juvenile hormone (JH) synthesis in insects. Consequently, they have been considered as potential lead compounds for the discovery of new insect growth regulators (IGRs). In the present work, receptor-based three-dimensional quantitative structure-activity relationship (3D-QSAR) was studied with 48 AST analogs, and a general approach for novel potent bioactive AST analogs is proposed. Hence, six novel AST analogs were designed and synthesized. Bioassays indicated that the majority novel analogs exhibited potent JH inhibitory activity, especially analog A6 (IC: 3.79 nmol/L), which can be used as lead compound to develop new IGRs.
阿特拉托菌素（AST）最初是作为昆虫保幼激素（JH）合成抑制剂而被描述的神经肽。因此，它们被认为是发现新的昆虫生长调节剂（IGRs）的潜在先导化合物。在本工作中，采用基于受体的三维定量构效关系（3D-QSAR）对 48 种 AST 类似物进行了研究，并提出了一种新型有效 AST 类似物的一般方法。因此，设计并合成了 6 种新型 AST 类似物。生物测定表明，大多数新型类似物均表现出较强的 JH 抑制活性，特别是类似物 A6（IC：3.79nmol/L），可作为先导化合物开发新型 IGRs。
