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 provide... More
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.
