Discovery of Pyrazole–Fusaric Acid Derivatives as the Potential Herbicidal Lead Compounds Targeting Both Transketolase and Protoporphyrinogen Oxidase
Yongqi Liu, Chengkun Li, Xizhe Ma, Zhitao Du, Chenhuan Wang, Dongchen Yang, Junmin Wang, Huaipu Yan, Jinlin Zhang, Yan-En WangAbstract
Transketolase (TKL, EC 2.2.1.1) was confirmed as a potential new target for herbicides. In this study, a series of pyrazole–fusaric acid derivatives 9a–9o were designed and synthesized via structural optimization of compound 7r. Among them, compound 9f exhibited good inhibition on Digitaria sanguinalis and Amaranthus retroflexus (inhibition >95%) even at 10 mg/L via the small cup method. It exhibited excellent inhibition against D. sanguinalis and A. retroflexus (inhibition >90%, 150 g ai/ha) via the pot bioassay superior to the positive control. Significantly, it showed good crop safety to maize, wheat, soybean, and cotton (the phytotoxicity <10%, 375 g ai/ha). Additionally, compound 9f exhibited excellent inhibition on both SvTKL and NtPPO (IC50: 0.11, 1.00 mg/L). Both molecular docking and molecular dynamics simulation confirmed that the complexes for SvTKL-9f and NtPPO-9f demonstrated strong stability. Altogether, there is potential to discover novel dual-target-inhibiting herbicide candidates by further structurally optimizing compound 9f.