Discovery of Mesoionic Derivatives Containing a Dithioacetal Skeleton as Novel Potential Antibacterial Agents and Mechanism Research

In
this study, the design and synthesis of novel pyrido­[1,2-a]­pyrimidinone mesoionic derivatives incorporating dithioacetal
structures were carried out. The three-dimensional quantitative structure–activity
relationship (3D-QSAR) model was built according to the EC50 values and directed the synthesis of compound A32.
The biological activity test against Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas oryzae pv. oryzicola (Xoc) indicated that compound A32 showed
good antibacterial activity with EC50 values of 10.9 and
17.5 mg/L, which were lower than the EC50 values of bismerthiazol
(29.3 and 39.8 mg/L) and thiodiazole copper (64.8 and 78.1 mg/L).
Furthermore, the in vivo antibacterial activity against bacterial
leaf blight (BLB) and bacterial leaf streak (BLS) revealed that the
protective activity of compound A32 was 43.9 and 41.7%,
respectively, which was better than the protective activity of thiodiazole
copper (40.6 and 35.0%). In addition, the protective activity against
bacterial leaf blight of compound A32 was associated
with the increasing rice defensive enzyme activity and the upregulation
of proteins involved in oxidative phosphorylation. Moreover, compound A32 could upregulate the expression of complex I (nicotinamide
adenine dinucleotide hydrogen (NADH) dehydrogenase) in the oxidative
phosphorylation pathway, which was verified by complex I activity
evaluation.