Targeting the virulence factors of
phytopathogenic bacteria is
an innovative strategy for alleviating or eliminating the pathogenicity
and rapid outbreak of plant microbial diseases. Therefore, several
types of 1,2,4-triazole thioethers bearing an amide linkage were prepared
and screened to develop virulence factor inhibitors. Besides, the
1,2,4-triazole scaffold was exchanged by a versatile 1,3,4-oxadiazole
core to expand molecular diversity. Bioassay results revealed that
a 1,2,4-triazole thioether A
10
bearing a privileged N-(3-nitrophenyl)acetamide
fragment was extremely bioactive against Xanthomonas
oryzae pv. oryzae (Xoo) with an EC50 value
of 5.01 μg/mL. Label-free quantitative proteomics found that
compound A
10
could significantly
downregulate the expression of Xoo’s type III secretion system
(T3SS) and transcription activator-like effector (TALE) correlative
proteins. Meanwhile, qRT-PCR detection revealed that the corresponding
gene transcription levels of these virulence factor-associated proteins
were substantially inhibited after being triggered by compound A
10
. As a result, the hypersensitive
response and pathogenicity were strongly depressed, indicating that
a novel virulence factor inhibitor (A
10
) was probably discovered. In vivo anti-Xoo trials displayed
that compound A
10
yielded practicable
control efficiency (54.2–59.6%), which was superior to thiadiazole-copper
and bismerthiazol (38.1–44.9%). Additionally, compound A
10
showed an appreciable antiviral
activity toward tobacco mosaic virus (TMV) with the curative and protective
activities of 54.6 and 76.4%, respectively, which were comparable
to ningnanmycin (55.2 and 60.9%). This effect was further validated
and visualized by the inoculation test using GFP-labeled TMV, thereby
leading to the reduced biosynthesis of green-fluorescent TMV on Nicotiana benthamiana. Given the outstanding features
of compound A
10
, it should be
deeply developed as a versatile agricultural chemical.