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

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 out-standing antibacterial activity against Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axono-podis pv. citri (Xac), and Pseudomonas syringae pv. actinidiae (Psa), with optimal EC50 values of 6.80 lg/mL (A9), 6.37 lg/mL (A9), and 10.75 lg/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 (nu-cleic 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 micro-bial diseases by targeting cell membranes. (c) 2023 The Authors. Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).