Department of Applied Chemistry, College of Science, China Agricultural University, Beijing, China.
State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection and Shenzhen Agricultural Genome Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China.
Pest Manag Sci. 2020 Sep;76(9):3030-3037. doi: 10.1002/ps.5852. Epub 2020 Apr 26.
Molting is an essential insect developmental process, in which a variety of enzymes are involved. The inhibition of these enzymes effect normal insect growth and development and may even cause death. OfHex1, one of the β-N-acetyl-D-hexosaminidases, is a key enzyme involved in the molting process of the Asian corn borer (Ostrinia furnacalis), and is deemed a potential insecticidal target.
Based on the crystal structure of OfHex1, virtual screening was carried out to obtain a novel class of OfHex1 inhibitors, of which, 28 compounds were subjected to bioactivity evaluation. The compound 3, N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)benzamide, showed good inhibition against OfHex1 with a K value of 11.2 μM. Structure optimization and molecular docking were applied for the structure-activity relationship analysis. The results also showed that the cyano group of this compound was essential for the maintenance of its inhibitory activity against OfHex1. Additionally, the interaction between this compound and Trp490, Glu328, Tyr475 and Trp524 were important for inhibitory activity.
The advantages of the derivatives of 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile, which have simple chemical structures and are easily synthesized, suggests them to be developed further as potential OfHex1 inhibitors for pest control. © 2020 Society of Chemical Industry.
蜕皮是昆虫发育过程中的一个重要过程，其中涉及多种酶。这些酶的抑制作用会影响昆虫的正常生长和发育，甚至可能导致死亡。OfHex1 是一种β-N-乙酰-D-己糖胺酶，是亚洲玉米螟蜕皮过程中的关键酶，被认为是一种潜在的杀虫靶标。
基于 OfHex1 的晶体结构，进行了虚拟筛选，获得了一类新型的 OfHex1 抑制剂，其中 28 种化合物进行了生物活性评价。化合物 3，N-(3-氰基-4,5,6,7-四氢苯并[b]噻吩-2-基)苯甲酰胺，对 OfHex1 表现出良好的抑制作用，K 值为 11.2 μM。进行了结构优化和分子对接以进行构效关系分析。结果还表明，该化合物的氰基对于维持其对 OfHex1 的抑制活性是必需的。此外，该化合物与 Trp490、Glu328、Tyr475 和 Trp524 之间的相互作用对于抑制活性很重要。
2-氨基-4,5,6,7-四氢苯并[b]噻吩-3-甲腈衍生物具有简单的化学结构，易于合成，具有优势，可进一步开发为防治害虫的潜在 OfHex1 抑制剂。 © 2020 英国化学学会。
