Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, Sichuan 610041, People's Republic of China.
Department of Chemical and Chemical Engineering, Hefei Normal University, Hefei, Anhui 230601, People's Republic of China.
J Agric Food Chem. 2020 May 27;68(21):5806-5815. doi: 10.1021/acs.jafc.0c00230. Epub 2020 May 13.
Our recent investigation on the insecticidal activities of several doramectin derivatives preliminarily revealed that the presence of hydrogen bonds at the C4″ position of the molecule with target protein γ-aminobutyric acid (GABA) receptor was crucial for retaining high insecticidal activity. As a continuation of our research work on the development of new insecticides, two series of novel acylurea and acylthiourea doramectin derivatives were designed and synthesized. The bioassay results indicated that the newly synthesized compounds (, , and ) exhibited higher insecticidal activity against diamondback moth, oriental armyworm, and corn borer than the control compounds doramectin, commercial avermectins, chlorbenzuron, and lead compound in our laboratory. Specifically, compound was identified as the most promising insecticide against diamondback moth, with a final mortality rate of 80.00% at the low concentration of 12.50 mg/L, showing approximately 7.75-fold higher potency than the parent doramectin (LC value of 48.1547 mg/L), 6.52-fold higher potency than commercial avermectins (LC value of 40.5507 mg/L), and 3.98-fold higher potency than compound (LC value of 24.7742 mg/L). Additionally, molecular docking simulations revealed that compound (2.17, 2.20, 2.56, and 2.83 Å) displayed stronger hydrogen-bond action in binding with the GABA receptor, better than that of compound (1.64 and 2.15 Å) and compound (2.20 and 2.31 Å) at the C4″ position. This work demonstrated that these compounds containing hydrogen-bond groups might contribute to the improvement of insecticidal activity and supply certain hints toward structure optimization design for the development of new insecticides.
我们最近对几种多拉菌素衍生物的杀虫活性进行了研究，初步表明，分子中与靶标蛋白γ-氨基丁酸（GABA）受体的 C4″位置形成氢键的存在对于保持高杀虫活性至关重要。作为我们开发新杀虫剂研究工作的延续，我们设计并合成了两个系列的新型酰基脲和酰基硫脲多拉菌素衍生物。生物测定结果表明，新合成的化合物（、和）对小菜蛾、东方粘虫和玉米螟的杀虫活性均高于对照化合物多拉菌素、市售阿维菌素、氯苯脲和我们实验室的先导化合物。具体而言，化合物被鉴定为最有前途的小菜蛾杀虫剂，在低浓度 12.50mg/L 时最终死亡率为 80.00%，比母体多拉菌素（LC 值为 48.1547mg/L）的活性高约 7.75 倍，比市售阿维菌素（LC 值为 40.5507mg/L）的活性高 6.52 倍，比化合物（LC 值为 24.7742mg/L）的活性高 3.98 倍。此外，分子对接模拟表明，化合物（2.17、2.20、2.56 和 2.83Å）在与 GABA 受体结合时表现出更强的氢键作用，优于化合物（1.64 和 2.15Å）和化合物（2.20 和 2.31Å）在 C4″位置的氢键作用。这项工作表明，这些含有氢键基团的化合物可能有助于提高杀虫活性，并为开发新杀虫剂的结构优化设计提供一定的启示。
