Investigations into Simplified Analogues of the Herbicidal Natural Product (+)‐Cornexistin

Abstract

We report the design, synthesis and biological evaluation of simplified analogues of the herbicidal natural product (+)‐cornexistin. Guided by an X‐Ray co‐crystal structure of cornexistin bound to transketolase from Zea mays, we attempted to identify the key interactions that are necessary for cornexistin to maintain its herbicidal profile. This resulted in the preparation of three novel analogues investigating the importance of substituents that are located on the nine‐membered ring of cornexistin. One analogue maintained a good level of biological activity and could provide researchers insights in how to further optimize the structure of cornexistin for commercialization in the future.

Discovery of Novel Pyrazole Acyl Thiourea Skeleton Analogue as Potential Herbicide Candidates

“…However, the protein crystal of SvTKL was not available until now, so a 3D homology model was constructed basing on the X-ray cocrystal structure of cornexistin diacid in complex with TKL from Zea mays (pdb: 8ci0) using the SWISS-MODEL platform, and the ligand-based docking pocket generation was conducted at the entrance to the TKL catalytic active site. 33 Crop Safety Test. Four major crops, maize, wheat, soybean, and cotton, were chosen as representatives of grain crops and cash crops to estimate the crop selectivity of the typical target compounds.…”

“…Molecular docking was performed to explore the possible interaction relationships between our title compounds and their potential target enzyme TKL. However, the protein crystal of Sv TKL was not available until now, so a 3D homology model was constructed basing on the X-ray cocrystal structure of cornexistin diacid in complex with TKL from Zea mays (pdb: 8ci0) using the SWISS-MODEL platform, and the ligand-based docking pocket generation was conducted at the entrance to the TKL catalytic active site …”