Wang Xin, Shuai Jing, Kong Yijin, Li Zhong, Li Weihua, Cheng Jiagao
Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
J Mol Graph Model. 2022 Nov;116:108257. doi: 10.1016/j.jmgm.2022.108257. Epub 2022 Jul 4.
The honey bee, Apis mellifera, shows variation in sensitivity to imidacloprid and thiacloprid, which does not reside at the target site but rather in the rapidly oxidative metabolism mediated by P450s (such as a single P450, CYP9Q3). An in silico study was conducted to investigate the various metabolism of imidacloprid and thiacloprid. The binding potency of thiacloprid was stronger and a stable π-π interaction with Phe121 and the N-H⋯N hydrogen bond with Asn214 are found in the CYP9Q3-thiacloprid system but absent in imidacloprid, which might affect the potential metabolic activity. Moreover, the values of highest occupied molecular orbit (HOMO) energy and the vertical ionization potential (IP) of two compounds demonstrated that thiacloprid is more likely to oxidation. The findings revealed the probable binding modes of imidacloprid and thiacloprid with CYP9Q3 and might facilitate future design of the low bee toxicity neonicotinoid insecticides.
蜜蜂（西方蜜蜂）对吡虫啉和噻虫啉的敏感性存在差异，这种差异并非存在于靶位点，而是在于由细胞色素P450（如单一的细胞色素P450，CYP9Q3）介导的快速氧化代谢过程中。开展了一项计算机模拟研究以探究吡虫啉和噻虫啉的各种代谢情况。噻虫啉的结合能力更强，在CYP9Q3-噻虫啉体系中发现了与苯丙氨酸121的稳定π-π相互作用以及与天冬酰胺214的N-H⋯N氢键，但在吡虫啉中不存在，这可能会影响潜在的代谢活性。此外，两种化合物的最高占据分子轨道（HOMO）能量值和垂直电离势（IP）表明，噻虫啉更易于被氧化。这些发现揭示了吡虫啉和噻虫啉与CYP9Q3可能的结合模式，并可能有助于未来低蜜蜂毒性新烟碱类杀虫剂的设计。
