Novel 2,5-dihydro-3H-[1,2,4]triazino[5,6-b]indole derivatives decorated with disulfide moiety are effective for treating bacterial infections by inducing reactive oxygen species.

BACKGROUND

Infectious diseases caused by pathogenic bacteria are the main causes of death in humans, and responsible for reduced yield quality and quantity of plants globally. This underscores the need for developing bactericide alternatives with novel modes-of-action.

RESULTS

Herein, we devised a series of novel 2,5-dihydro-3H-[1,2,4]triazino[5,6-b]indole derivatives decorating with the disulfide moiety (W1-W36). Bioassay results indicated their antibacterial activity against three pathogenic bacteria [Xoo (Xanthomonas oryzae pv. oryzae), Xac (Xanthomonas axonopodis pv. citri) and Psa (Pseudomonas syringae pv. actinidiae)]. Compound W1 demonstrated eminent anti-Xoo activity in vitro, with a median effecgtive concentration (EC50) value of 0.77 μg mL-1, which was considerably higher than that of the reference agent thiodiazole copper (TC, EC50 = 104 μg mL-1). At 200 μg mL-1, compound W1 demonstrated better in vivo control efficiency (46.09% curative activity; 51.26% protective activity) toward rice bacterial blight diseases, with a >20% increase in activity relative to that of the control TC. Mechanistic studies revealed that compound W1 enabled the suppression of the activities of oxidoreductases including superoxide dismutase and catalase, disrupted the redox balance, and ultimately induced bacterial cell apoptosis.

CONCLUSION

Overall, these new molecules were characterized by high antibacterial ability, reactive oxygen species targeting performance, and low toxicity. They demonstrated unprecedented potential for controlling bacterial infection. © 2025 Society of Chemical Industry.