Ion exchange pattern-based 18β-glycyrrhetinic acid containing pyridinium salts derivatives as novel antibacterial agents with low toxicity

Abstract

Studies in the past few years have shown that simple salts, such as pyridinium salts and imidazole salts, have excellent antibacterial activity. However, their application in drugs and agrichemicals development has been limited due to their high toxicity. In this study, we found that synthesized target compounds with pyridinium salt unit A1 and B6 displayed excellent anti-Xac (Xanthomonas. axonopodis pv. citri) and Xoo (Xanthomonas oryzae pv. oryzae) activity, with EC50 values of 7.67 μg/mL and 1.37 μg/mL, respectively. On searching for a toxicity reduction strategy, an ion exchange method was adopted to obtain a new type of various organic acid-decorated pyridinium salt derivatives containing with glycyrrhetinic acid framework, and their structure was characterized by FTIR and 1H NMR. Furthermore, bioassays and toxicity tests were used to show that these organic acid-exchanged compounds not only exhibited lower toxicity to plants but also had excellent antibacterial activity towards virulent phytopathogenic bacteria, especially compound D3, which provided an EC50 of 1.60 μg/mL toward Xoo. Subsequently, the pot experiments determined that compound D3 exhibited suitable protective and curative activities for the management of rice bacterial leaf blight at 200 μg/mL, with control efficacies of 54.09% and 38.50%, respectively. In addition, studies evaluating potential antibacterial mechanisms suggested that apoptosis was responsible for the antibacterial behavior of the target compounds. Overall, this study proved that the ion exchange method was a feasible strategy to reduce the toxicity of pyridinium salts and was promising for use in the development of novel antimicrobial agents.

Keywords

• Pyridinium salts
• Phytotoxicity
• Ion exchange strategy
• Antibacterial activity