A total of 35 new quinazolinone derivatives bearing the 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole scaffold and the 4-piperidinyl linker were designed, prepared, and assessed for their antibacterial and antifungal activities. Among these derivatives, the chemical structure of compound F5 was clearly verified via single-crystal X-ray diffraction analysis. The experimental results revealed that some of the compounds displayed good even excellent inhibitory effects toward the tested phytopathogenic bacteria. For instance, compound F33 was capable of strongly inhibiting Xanthomonas oryzae pv. oryzae (Xoo) in vitro with an EC50 (half-maximal effective concentration) value of 4.1 μg/mL, about 16-fold more effective than the commercialized bactericide bismerthiazol. Significantly, this compound also effectively suppressed the proliferation of Xoo in the potted rice plants, showing a good in vivo protection efficacy of 47.6% at 200 μg/mL. Subsequently, the antibacterial mechanisms of compound F33 were explored by means of different biophysical and biochemical methods. Last, some of the compounds were found to possess relatively good antifungal activities in vitro, like compound F19 against Phytophthora nicotianae (with an inhibition rate of 67.2% at 50 μg/mL). In a word, the current experimental results imply that the 4-piperidinyl-bridged quinazolinone-1,2,4-triazolo[3,4-b][1,3,4]thiadiazole derivatives possess potential as lead compounds for developing more efficient anti-Xoo bactericides.
Keywords: 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole; antibacterial mechanisms; antimicrobial activities; preparation; quinazolinone; structure–activity relationship (SAR).