Laboratory of Pharmaceutical Design and Synthesis, College of Sciences, Northwest A&F University , Yangling 712100, Shaanxi Province, People's Republic of China.
J Agric Food Chem. 2013 Jun 19;61(24):5696-705. doi: 10.1021/jf400536q. Epub 2013 Jun 5.
In continuation of our program aimed at the discovery and development of natural-product-based pesticidal agents, 54 novel N-arylsulfonyl-3-acylindole arylcarbonyl hydrazone derivatives were prepared, and their structures were well characterized by ¹H NMR, ¹³C NMR, HRMS, ESI-MS, and mp. Their nematicidal activity was evaluated against that of the pine wood nematode, Bursaphelenchus xylophilus in vivo. Among all of the derivatives, especially V-12 and V-39 displayed the best promising nematicidal activity with LC₅₀ values of 1.0969 and 1.2632 mg/L, respectively. This suggested that introduction of R¹ and R² together as the electron-withdrawing substituents, R³ as the methyl group, and R⁴ as the phenyl with the electron-donating substituents could be taken into account for further preparation of these kinds of compounds as nematicidal agents. Six selected descriptors are a WHIM descriptor (E1m), two GETAWAY descriptors (R1m+ and R3m+), a Burden eigenvalues descriptor (BEHm8), and two edge-adjacency index descriptors (EEig05x and EEig13d). Quantitative structure-activity relationship (QSAR) studies demonstrated that the structural factors, such as molecular mass (a negative correlation with the bioactivity) and molecular polarity (a positive correlation with bioactivity), are likely to govern the nematicidal activities of these compounds. For this model, the correlation coefficient (R²(training set)), the leave-one-out cross-validation correlation coefficient (Q²(LOO)), and the 7-fold cross-validation correlation coefficient (Q²(7-fold)) were 0.791, 0.701, and 0.715, respectively. The external cross-validation correlation coefficient (Q²ext) and the root-mean-square error for the test set (RMSE(test set)) were 0.774 and 3.412, respectively. This study will pave the way for future design, structural modification, and development of indole derivatives as nematicidal agents.
作为我们发现和开发基于天然产物的杀虫剂计划的延续，我们制备了 54 种新型 N-芳基磺酰基-3-乙酰基吲哚芳甲酰腙衍生物，并通过¹H NMR、¹³C NMR、HRMS、ESI-MS 和 mp 对其结构进行了很好的表征。它们的杀线虫活性在体内针对松材线虫进行了评估。在所有衍生物中，特别是 V-12 和 V-39 表现出最好的杀线虫活性，LC₅₀ 值分别为 1.0969 和 1.2632 mg/L。这表明，同时引入 R¹ 和 R² 作为吸电子取代基，R³ 为甲基，R⁴ 为带有供电子取代基的苯基，可以考虑进一步制备这类化合物作为杀线虫剂。六个选定的描述符是 WHIM 描述符（E1m）、两个 GETAWAY 描述符（R1m+和 R3m+）、一个 Burden 特征值描述符（BEHm8）和两个边缘邻接指数描述符（EEig05x 和 EEig13d）。定量构效关系（QSAR）研究表明，结构因素，如分子质量（与生物活性呈负相关）和分子极性（与生物活性呈正相关），可能控制这些化合物的杀线虫活性。对于该模型，相关系数（R²（训练集））、留一法交叉验证相关系数（Q²（LOO））和 7 倍交叉验证相关系数（Q²（7 倍））分别为 0.791、0.701 和 0.715。外部交叉验证相关系数（Q²ext）和测试集的均方根误差（RMSE（测试集））分别为 0.774 和 3.412。这项研究将为未来设计、结构修饰和开发吲哚衍生物作为杀线虫剂铺平道路。
