ABSTRACT
Coronatine-insensitive 1 (COI1) has been identified as a target receptor of plant elicitor coronatine (COR). To discover novel plant elicitor leads, most of the potential molecules among 129 compounds discovered from the ZINC database by docking based virtual screening targeting COI1 were quinoline amides. On this lead basis, 2-benzothiadiazolylquinoline-4-carboxamides were rationally designed and synthesized for bioassay. All target compounds did not show significantly in vitro antifungal activity, compounds 4d, 4e and 4o displayed good in vivo systemic acquired resistance activity for Arabidopsis thaliana against Hyaloperonospora arabidopsidis isolate Noco2 with over 80% of inhibitory rate at the concentration of 50 µM. These results indicate that 2-benzothiadiazolylquinoline-4-carboxamides are promising plant elicitor leads for further study.
ABSTRACT
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. YZK-C22, which contains a 1,2,3-thiadiazol-[1,2,4]triazolo[3,4-b][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-b][1,3,4]thiadiazole scaffold exhibited good antifungal activity. Inspired by this, a series of pyrrolo[2,3-d]thiazole derivatives were designed and synthesized through a bioisosteric strategy. Compounds C1, C9, and C20 were found to be more active against Rhizoctonia solani than the positive control YZK-C22. More than half of the target compounds provided favorable activity against Botrytis cinerea, where the EC50 values of compounds C4, C6, C8, C10, and C20 varied from 1.17 to 1.77 µg/mL. Surface plasmon resonance and molecular docking suggested that in vitro potent compounds C9 and C20 have a new mode of action instead of acting as pyruvate kinase inhibitors. Transcriptome analysis revealed that compound C20 can impact the tryptophan metabolic pathway, cutin, suberin, and wax biosynthesis of B. cinerea. Overall, pyrrolo[2,3-d]thiazole is discovered as a new fungicidal lead structure with a potential new mode of action for further exploration.
Subject(s)
Botrytis , Fungicides, Industrial , Rhizoctonia , Thiazoles , Tryptophan , Waxes , Fungicides, Industrial/pharmacology , Fungicides, Industrial/chemistry , Fungicides, Industrial/chemical synthesis , Rhizoctonia/drug effects , Botrytis/drug effects , Thiazoles/pharmacology , Thiazoles/chemistry , Thiazoles/metabolism , Tryptophan/metabolism , Tryptophan/chemistry , Waxes/chemistry , Waxes/metabolism , Structure-Activity Relationship , Metabolic Networks and Pathways/drug effects , Molecular Docking Simulation , Pyrroles/pharmacology , Pyrroles/chemistry , Pyrroles/metabolism , Plant Diseases/microbiology , Molecular StructureABSTRACT
To increase the structural diversity of insecticides and meet the needs of effective integrated insect management, the structure of chlorantraniliprole was modified based on a previously established three-dimensional quantitative structure-activity relationship (3D-QSAR) model. The pyridinyl moiety in the structure of chlorantraniliprole was replaced with a 4-fluorophenyl group. Further modifications of this 4-fluorophenyl group by introducing a halogen atom at position 2 and an electron-withdrawing group (e.g., iodine, cyano, and trifluoromethyl) at position 5 led to 34 compounds with good insecticidal efficacy against Mythimna separata, Plutella xylostella, and Spodoptera frugiperda. Among them, compound IV f against M. separata showed potency comparable to that of chlorantraniliprole. IV p against P. xylostella displayed a 4.5 times higher potency than chlorantraniliprole. In addition, IV d and chlorantraniliprole exhibited comparable potencies against S. frugiperda. Transcriptome analysis showed that the molecular target of compound IV f is the ryanodine receptor. Molecular docking was further performed to verify the mode of action and insecticidal activity against resistant P. xylostella.