Discovery of Indole-3-acetamide Derivatives as Potent Transketolase-Inhibiting-Based Herbicidal Leads

作者：Yan‐En Wang, Chengkun Li, Shuang Cao, Jiayao Li, Dongyang Li, Z. Z. Du, Peng Li, Junmin Wang, Haijiao Dong, Dongchen Yang, Zexiu An, Jinlin Zhang · 发表于：Journal of Agricultural and Food Chemistry · 年份：2025 · DOI：10.1021/acs.jafc.5c01085 · 被引用次数：5 · 研究领域：Biochemical Acid Research Studies、Microbial Metabolic Engineering and Bioproduction、Plant biochemistry and biosynthesis

Transketolase (TKL; EC 2.2.1.1) has been identified as a potential new target for the development of novel herbicides. To discover natural product-based transketolase inhibitors with high herbicidal activity, some 9H-pyrido[3,4- b ]indoles ( I) targeting Sv TKL were obtained from the biogenic library of ZINC20 using a structure-based virtual screening (SBVS) methodology. Then, a series of indole-3-acetamides 7a – 7x were designed by structural optimization of compounds I, synthesized, and subjected to bioassay. Among them, compound 7m exhibited the best herbicidal efficacy against Digitaria sanguinalis ( D. sanguinalis ) and Amaranthus retroflexus ( A. retroflexus ) by both the small cup method (with an inhibition rate of over 95% at 100 mg/L) and the foliar spray method (with an inhibition rate of over 90% at 175 g (a.i.)/ha). Furthermore, compound 7m was safe for maize, wheat, soybean, and cotton (with phytotoxicity less than 10%) at a dosage of 375 g (a.i.)/ha. Both fluorescence quenching and Sv TKL inhibitory experiments showed that compound 7m was a typical Sv TKL inhibitor. A molecular docking study further verified that compound 7m exhibited higher binding affinity with Sv TKL, which contributed to its higher inhibitory activity on Sv TKL. Molecular dynamics simulation was also performed to explore the dynamic stability of 7m- Sv TKL complexes. Additionally, the DFT properties of compound 7m further supported its superior activity against Sv TKL. Taken together, compou...