New Lead Discovery of Herbicide Safener for Metolachlor Based on a Scaffold-Hopping Strategy

• Published in: Molecules (Basel, Switzerland) Vol. 25; no. 21; p. 4986
• Main Authors: Deng, Xile, Zheng, Wenna, Zhan, Qingcai, Deng, Yanan, Zhou, Yong, Bai, Lianyang
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28.10.2020; MDPI
• Subjects: Acetamides - adverse effects; Acylation; Agricultural land; Agricultural production; Amines; Animals; Aquatic organisms; Aquatic plants; Biological activity; Carbon; Catalase; Commercialization; Crops; Dose-Response Relationship, Drug; Drug Discovery - methods; Enzymes; Glutathione transferase; herbicide safener; Herbicides; Herbicides - adverse effects; Mass spectrometry; Mass spectroscopy; Metolachlor; N-alkylamides; natural products; NMR; Nuclear magnetic resonance; Optimization; Oryza - drug effects; Peroxidase; Pesticides; Phytotoxicity; Plant protection; Polyphenol oxidase; Rice; Safety; sanshools; Scaffolds; Seedlings; Spices; Superoxide dismutase; synthesis; Zanthoxylum; Zebrafish - embryology; synthesis; natural products; N-alkylamides; sanshools; herbicide safener
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25214986

The use of herbicide safeners can significantly alleviate herbicide injury to protect crop plants and expand the application scope of the existing herbicides in the field. Sanshools, which are well known as spices, are -alkyl substituted compounds extracted from the species and have several essential physiological and pharmacological functions. Sanshools display excellent safener activity for the herbicide metolachlor in rice seedlings. However, the high cost of sanshools extraction and difficulties in the synthesis of their complicated chemical structures limit their utilization in agricultural fields. Thus, the present study designed and synthesized various -alkyl amide derivatives via the scaffold-hopping strategy to solve the challenge of complicated structures and find novel potential safeners for the herbicide metolachlor. In total, 33 -alkyl amide derivatives ( - , - , and - ) were synthesized using amines and saturated and unsaturated fatty acids as starting materials through acylation and condensation. The identity of all the target compounds was well confirmed by H-NMR, C-NMR, and high-resolution mass spectrometry (HRMS). The primary evaluation of safener activities for the compounds by the agar method indicated that most of the target compounds could protect rice seedlings from injury caused by metolachlor. Notably, compounds and displayed excellent herbicide safener activities on plant height and demonstrated relatively similar activities to the commercialized compound dichlormid. Moreover, we showed that compounds and had higher glutathione -transferase (GST), superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and polyphenol oxidase (PPO) activities in rice seedlings, compared to the metolachlor treatment. In particular, and are safer for aquatic organisms than dichlormid. Results from the current work exhibit that compounds and have excellent crop safener activities toward rice and can, thus, be promising candidates for further structural optimization in rice protection.