Design, Synthesis, Antibacterial, and Antifungal Activity Evaluation of 1,3,4-Oxadiazole Thioether Derivatives Incorporating a Methylsulfonyl Moiety

Abstract

In this study, a series of novel 1,3,4-oxadiazole thioether derivatives incorporating a methylsulfonyl moiety were synthesized and their structures were characterized by ¹H, ¹³C NMR, and HRMS. Bioassay results demonstrated that the target compounds exhibited moderate to good in vitro antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri (Xac), and Wickerhamomyces anomalus (Wa). Notably, 2-[(4-fluorobenzyl)thio]-5-[4-(methylsulfonyl)phenyl]-1,3,4-oxadiazole showed excellent antibacterial activities against these pathogens at concentrations of 200 and 100 μg/mL, with inhibition rates of 90 and 76% for Xoo, 84 and 64% for Xac, and 96 and 81% for Wa, respectively, which were even better than thiodiazole copper. However, the target compounds exhibited certain in vitro antifungal activities against Penicillium sumatraense (Ps) and Aspergillus fumigatus (Af) at 50 μg/mL, with the inhibition rates of 25–46 and 18–42%, respectively, which were lower than those of prochloraz. To the best of our knowledge, it is the first report on the synthesis and bioactivity evaluation of this series of 1,3,4-oxadiazole thioether derivatives incorporating a methylsulfonyl moiety.