title: Design, Synthesis, Fungicidal Activity, and Unexpected Docking Model of the First Chiral Boscalid Analogues Containing Oxazolines.
abstract: Chirality greatly influences the biological and pharmacological properties of a pesticide and will contribute to unnecessary environmental loading and undesired ecological impact. No structure and activity relationship (SAR) of enantiopure succinate dehydrogenase inhibitors (SDHIs) was documented during the structure optimization of boscalids. On the basis of commercial SDHIs, oxazoline natural products, and versatile oxazoline ligands in organic synthesis, the first effort was devoted to explore the chiral SDHIs and the preliminary mechanism thereof. Fine-tuning furnished chiral nicotinamides 4ag as a more promising fungicidal candidate against Rhizoctonia solani, Botrytis cinerea, and Sclerotinia sclerotiorum, with EC50values of 0.58, 0.42, and 2.10 mg/L, respectively. In vivo bioassay and molecular docking were investigated to explore the potential in practical application and plausible novelty in action mechanism, respectively. The unexpected molecular docking model showed the different chiral effects on the binding site with the amino acid residues. This chiral nicotinamide also featured easy synthesis and cost-efficacy. It will provide a powerful complement to the commercial SDHI fungicides with the introduction of chirality.
authors: Department of Pesticide Science, College of Plant Protection, Nanjing Agricultural University , Weigang 1, Xuanwu District, Nanjing, Jiangsu 210095, People's Republic of China.
authors: Shengkun
authors: S
authors: Li
authors: Department of Pesticide Science, College of Plant Protection, Nanjing Agricultural University , Weigang 1, Xuanwu District, Nanjing, Jiangsu 210095, People's Republic of China.
authors: Dangdang
authors: D
authors: Li
authors: Department of Pesticide Science, College of Plant Protection, Nanjing Agricultural University , Weigang 1, Xuanwu District, Nanjing, Jiangsu 210095, People's Republic of China.
authors: Taifeng
authors: T
authors: Xiao
authors: Department of Pesticide Science, College of Plant Protection, Nanjing Agricultural University , Weigang 1, Xuanwu District, Nanjing, Jiangsu 210095, People's Republic of China.
authors: ShaSha
authors: S
authors: Zhang
authors: Department of Pesticide Science, College of Plant Protection, Nanjing Agricultural University , Weigang 1, Xuanwu District, Nanjing, Jiangsu 210095, People's Republic of China.
authors: Zehua
authors: Z
authors: Song
authors: Department of Pesticide Science, College of Plant Protection, Nanjing Agricultural University , Weigang 1, Xuanwu District, Nanjing, Jiangsu 210095, People's Republic of China.
authors: Hongyu
authors: H
authors: Ma
mesh_terms: D001203:Ascomycota / Q000187:drug effects; D001713:Biphenyl Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D020171:Botrytis / Q000187:drug effects*; D015195:Drug Design; D005659:Fungicides, Industrial / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D012232:Rhizoctonia / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D001713:Biphenyl Compounds; D005659:Fungicides, Industrial; D009536:Niacinamide; C550088:2-chloro-N-(4-chlorobiphenyl-2-yl)nicotinamide
keywords: chiral pesticide; fungicide; nicotinamide; oxazoline; spoxazomicin