Discovery of novel 3-(piperazin-1-yl)propan-2-ol decorated carbazole derivatives as new membrane-targeting antibacterial agents

Abstract

The increasing resistance problems of pathogens have drastically reduced the efficiency of existing drugs and agricultural chemicals, increasing the difficulty of preventing and controlling bacterial diseases. To create effective bactericide alternatives, a series of novel 3-(piperazin-1-yl)propan-2-ol decorated carbazole derivatives was fabricated, and their bioactivities and drug-likeness properties were evaluated. The in vitro bioassays showed that target molecules had outstanding antibacterial activity against Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri (Xac), and Pseudomonas syringae pv. actinidiae (Psa), with optimal EC50 values of 6.80 μg/mL (A9), 6.37 μg/mL (A9), and 10.75 μg/mL (A10), respectively. Furthermore, a series of biochemical assays indicated that title molecules could negatively impact the function of bacteria by irreversibly damaging their cell membranes, resulting in cytoplasmic components leakage (nucleic acids and proteins). In addition, phytotoxicity test and in silico toxicity predictions suggested that compound A9 had low phytotoxicity, and possessed acceptable drug-like properties. Our results showed that carbazole derivatives containing an 3-(piperazin-1-yl)propan-2-ol moiety were promising skeletons to develop novel bactericides with low toxicity for controlling refractory microbial diseases by targeting cell membranes.

Keywords

• Carbazole derivatives
• Cell membrane
• Toxicity
• Microbial diseases
• Drug discovery