Department of Chemistry, Punjab Agricultural University, Ludhiana 141004, Punjab, India.
Department of Chemistry, Punjab Agricultural University, Ludhiana 141004, Punjab, India.
Pestic Biochem Physiol. 2021 Jan;171:104736. doi: 10.1016/j.pestbp.2020.104736. Epub 2020 Oct 22.
Meloidogyne incognita is an economically dominant pathogen infesting a wide range of crops curbing their growth and productivity. Deregistration of frontline nematicides has necessitated exploration of innovative and novel class of structurally diverse nematicides with streamlined activity. In this context, N-alkylated derivatives of isatin known for their remarkable biological profile were synthesized, characterized and evaluated in vitro for their antinemic character followed by in silico studies for their mode of action and toxicological studies for their fitness as agrochemical. The antinemic evaluation was carried by egg hatch inhibition and juvenile mortality and its effect on egg hatching. Compounds 1 and 2a exhibited nematicidal potential and significantly decreased egg hatching and increased juvenile mortality. For egg hatch inhibition LC and LC values for 1 were found to be 0.125 and 1.380 mg/ml and for compound 2a, 0.457 and 8.511 mg/ml respectively. For juvenile mortality LC and LC values for 1 were found to be 0.109 and 0.776 mg/ml and for 2a, 0.190 and 1.380 mg/ml respectively. For insights into the mode of action of the synthesized molecules, in silico studies for the targeted effects were conducted which revealed novel interaction with pathogenic protein - Aspartyl protease. Computational studies on the drug-ability and potential toxicity of the selected compounds revealed they belonged to class IV and are safe. With good reasons, our compounds hold value for their exploration in agrochemical industry and thus, this study identifies a new scaffold with useful level of nematicidal activity for its use in agriculture industry.
南方根结线虫是一种经济上占主导地位的病原体，它侵害范围广泛的作物，抑制其生长和生产力。由于前沿杀线虫剂的撤销登记，因此需要探索具有创新性和新颖结构多样化的杀线虫剂，这些杀线虫剂具有简化的活性。在这种情况下，合成了具有显著生物学特性的色胺 N-烷基化衍生物，并对其进行了体外抗线虫特性评价，随后进行了作用模式的计算机研究和毒理学研究，以评估其作为农用化学品的适应性。通过卵孵化抑制和幼虫死亡率及其对卵孵化的影响来进行抗线虫评价。化合物 1 和 2a 表现出杀线虫潜力，显著降低了卵孵化率，增加了幼虫死亡率。对于卵孵化抑制，化合物 1 的 LC 和 LC 值分别为 0.125 和 1.380 mg/ml，化合物 2a 的 LC 和 LC 值分别为 0.457 和 8.511 mg/ml。对于幼虫死亡率，化合物 1 的 LC 和 LC 值分别为 0.109 和 0.776 mg/ml，化合物 2a 的 LC 和 LC 值分别为 0.190 和 1.380 mg/ml。为了深入了解合成分子的作用模式，对靶标效应进行了计算机研究，结果表明与致病蛋白天冬氨酸蛋白酶有新的相互作用。对所选化合物的药物特性和潜在毒性的计算研究表明，它们属于第 IV 类，是安全的。有充分的理由表明，我们的化合物因其在农业化学工业中的探索价值而具有价值，因此，这项研究为农业工业提供了一种具有有用的杀线虫活性水平的新支架。
