Design, synthesis, crystal structure, and in vitro antibacterial activities of sulfonamide derivatives bearing the 4-aminoquinazoline moiety.

ABSTRACT

A total of 66 sulfonamide derivatives bearing the 4-aminoquinazoline moiety were designed and synthesized, and their structures were fully characterized by 1H NMR, 13C NMR, and HRMS techniques. Among them, the structures of compounds 5A10 and 5B11 were further confirmed through X-ray single-crystal diffraction analyses. The bioassay results indicated that some of the target compounds displayed higher inhibition activities in vitro against the tested phytopathogenic bacteria. For example, compound 5A26 exhibited a strong anti-Xanthomonas oryzae pv. oryzicola (Xoc) efficacy with an EC50 (half-maximal effective concentration) value of 30.6 µg/mL, over twofold more active than control agent bismerthiazol (BMT). Additionally, compound 5B14 had a good antibacterial effect against the phytopathogen Xanthomonas axonopodis pv. citric (Xac) with EC50 = 34.5 µg/mL, significantly better than control agent BMT (71.5 µg/mL). The anti-Xoc mechanistic studies showed that compound 5A26 exerted its antibacterial efficacy by increasing the permeability of bacterial membrane, decreasing the content of extracellular polysaccharides, and triggering morphological changes of bacterial cells.