Design, Synthesis And Antibacterial Activity Of Novel Piperidine Derivatives Containing Amide/sulfonamide Structure

Plant bacterial diseases are an increasing problem and they develop strong resistances for traditional pesticides,restricting the quality and yield of agricultural products around the world,and causing the food supply and food safety are hardly ensured.To develop low-risk and high-efficiency agrochemical alternatives with novel modes of action,a novel series of piperidine derivatives containing amide and sulfanilamide fragment were designed and synthesized and assessed their antibacterial potency against two plant pathogen Xanthomonas.The bioassay results revealed that most molecules displayed excellent in vitro antibacterial potency towards Xanthomonas oryzae pv.oryzae（Xoo）and Xanthomonas axonopodis pv.citri（Xac）.In particular,molecule D₄ exhibited outstanding inhibitory activity toward Xoo with EC₅₀ value of 2.02μg/m L,which was quite better than those of the commercial agents bismerthiazol(EC₅₀=42.38μg/m L)and thiodiazole copper(EC₅₀=64.50μg/m L).Besides,compound C₈ displayed the best inhibitory activity against Xac,with an EC₅₀ value of 4.74μg/m L,which was superior to the bismerthiazol(EC₅₀=110.54μg/m L)and thiodiazole copper(EC₅₀=121.40μg/m L).In vivo assays toward rice bacterial blight showed that the molecule D₄ presented acceptable curative and protection activities of 34.78%,and 39.83%at 200μg/m L,which were greater than thiodiazole（curative and protection activities of 29.57%and 30.51%,respectively）and comparable to those of bismerthiazol（curative and protection activities of 33.91%and38.14%,respectively）.Scanning electron microscope analysis,propidium iodide（PI）staining,electric conductivity,and protein leakage assays confirmed that compound D₄increased cell membrane permeability and irreversibly damaged the cell membrane.Molecular docking study indicated that molecule D₄ could form strong interactions with residues ASP-264,ALA-267,and GLN-55 of the Xoo dihydropteroate synthase.This study highlights the valuable insights for the excavation and development of new bactericides that can concurrently serve as dihydropteroate synthase inhibitors and targeting-cell membrane agents.