Novel 1,2,4-oxadiazole derivatives containing a sulfone moiety: Design, synthesis, biological activity, and antivirulence factors.

Abstract

To discover novel antibacterial agents, a series of 28 1,2,4-oxadiazole derivatives containing sulfone moiety were designed, synthesized, and evaluated for their antibacterial activity. Some of the target compounds exhibited promising antibacterial properties. Among them, compound G26 showed excellent activity against Xanthomonas oryzae pv. oryzae (Xoo), with an EC₅₀ value of 24.3 mg/L, which was superior to the positive control agents bismerthiazol (EC₅₀ = 54.1 mg/L) and thiodiazole copper (EC₅₀ = 92.3 mg/L). Compound G26 exhibited a protective efficacy of 30.9% against rice bacterial leaf blight, which was comparable to that of thiodiazole copper (31.2%) but lower than that of bismerthiazol (48.7%). Mechanistically, G26 inhibited the growth and proliferation of Xoo by suppressing virulence factors (including extracellular polysaccharides, cell membrane integrity, motility, xanthomonadin, and extracellular amylase), increasing membrane permeability, and altering the bacterial surface morphology, ultimately leading to bacterial death. In addition, some of the compounds demonstrated good antifungal activity. Specifically, compounds G6, G9, G12, and G17 exhibited EC₅₀ values of 25.7, 17.7, 29.5, and 24.3 mg/L, respectively, against Botrytis cinerea, outperforming the commercial fungicide fluopyram (EC₅₀ = 106.7 mg/L). Compound G26 may serve as a lead compound for the development of new antibacterial agents through further structural optimization.