State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, P. R. China.
Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, No. 94, Weijin Road, Nankai District, Tianjin 300071, P. R. China.
J Agric Food Chem. 2024 May 29;72(21):11990-12002. doi: 10.1021/acs.jafc.4c00930. Epub 2024 May 17.
The main challenge in the development of agrochemicals is the lack of new leads and/or targets. It is critical to discover new molecular targets and their corresponding ligands. , which contains a 1,2,3-thiadiazol-[1,2,4]triazolo[3,4-][1,3,4]thiadiazole skeleton, is a fungicide lead compound with broad-spectrum fungicidal activity. Previous studies suggested that the [1,2,4]triazolo[3,4-][1,3,4]thiadiazole scaffold exhibited good antifungal activity. Inspired by this, a series of pyrrolo[2,3-]thiazole derivatives were designed and synthesized through a bioisosteric strategy. Compounds , , and were found to be more active against than the positive control YZK-C22. More than half of the target compounds provided favorable activity against , where the EC values of compounds , , , , and varied from 1.17 to 1.77 μg/mL. Surface plasmon resonance and molecular docking suggested that potent compounds and have a new mode of action instead of acting as pyruvate kinase inhibitors. Transcriptome analysis revealed that compound can impact the tryptophan metabolic pathway, cutin, suberin, and wax biosynthesis of . Overall, pyrrolo[2,3-]thiazole is discovered as a new fungicidal lead structure with a potential new mode of action for further exploration.
农用化学品开发面临的主要挑战是缺乏新的先导化合物和/或靶标。发现新的分子靶标及其相应配体至关重要。 ，含有 1,2,3-噻二唑-[1,2,4]三唑-[3,4-][1,3,4]噻二唑骨架，是一种具有广谱杀菌活性的杀菌剂先导化合物。先前的研究表明，[1,2,4]三唑-[3,4-][1,3,4]噻二唑支架表现出良好的抗真菌活性。受此启发，通过生物等排策略设计并合成了一系列吡咯并[2,3-]噻唑衍生物。发现化合物 、 和 对 的活性高于阳性对照 YZK-C22。超过一半的目标化合物对 表现出良好的活性，化合物 、 、 、 和 的 EC 值在 1.17 到 1.77 μg/mL 之间。表面等离子体共振和分子对接表明，有效化合物 和 具有新的作用模式，而不是作为丙酮酸激酶抑制剂。转录组分析表明，化合物 可以影响 的色氨酸代谢途径、角质、木栓质和蜡生物合成。总体而言，吡咯并[2,3-]噻唑被发现是一种新的杀菌先导结构，具有潜在的新作用模式，值得进一步探索。
