Because only a handful of agrochemicals can manage bacterial
infections,
the discovery and development of innovative, inexpensive, and high-efficiency
antibacterial agents targeting these infections are challenging. Herein,
a series of novel epimeric and chiral 18β-glycyrrhetinic acid
(GA) ester derivatives with various tertiary amine pendants were designed,
synthesized, and screened for pharmacological activity. Results showed
that some of the title compounds were conferred with significantly
enhanced antibacterial activity toward phytopathogens Xanthomonas
oryzae pv oryzae (A
2
, B
1
–B
3
, and C
1
, EC50 values within 3.81–4.82 μg/mL)
and Xanthomonas axonopodis pv citri (B
1
, EC50 = 3.18
μg/mL; B
2
, EC50 = 2.76 μg/mL). These activities are superior to those of GA
(EC50 > 400 μg/mL), thiodiazole copper, and bismerthiazol.
Pharmacophore studies revealed that the synergistic combination of
GA skeleton and tertiary amine scaffolds contributed to the biological
actions. In vivo experiments displayed their promising applications
in controlling bacterial infections. Antibacterial mechanism studies
revealed that the title compounds could trigger apoptosis in the tested
pathogens, evident by bacteria morphological changes observed in scanning
electron microscopy images. This outcome should motivate the development
of various apoptosis inducers against plant bacterial diseases by
a novel mode of action compared to that of existing agricultural chemicals.
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