Abstract：
Due to antibiotic overuse, many bacteria have developed resistance, creating an urgent need for novel antimicrobial agents. It has been established that the filamentous temperature-sensitive mutant Z (FtsZ) of the bacterial cell division protein is an effective and promising antibacterial target. In this study, the optimal proteins were assessed by early recognition ability and the processed compound libraries were virtually screened using Vina. This effort resulted in the identification of 14 potentially active antimicrobial compounds. Among them, the compound T5S1607 demonstrated remarkable antibacterial efficacy against Bacillus subtilis ATCC9732 (MIC = 1 μg/mL) and Staphylococcus aureus ATC5C6538 (MIC = 4 μg/mL). Furthermore, in vitro experiments demonstrated that the selected compound T5S1607 rapidly killed bacteria and induced FtsZ protein aggregation, preventing bacterial division and leading to bacterial death. Additionally, cell toxicity and hemolysis experiments indicate that compound T5S1607 exhibits minimal toxicity to LO2 cells and shows no significant hemolytic effects on mammalian cells in vitro at the MIC concentration range. All the results indicate that compound T5S1607 is a promising antibacterial agent and a potential FtsZ inhibitor. In conclusion, this work successfully discovered FtsZ inhibitors with good activity through the virtual screening drug discovery process.
摘要：
由于抗生素的过度使用，许多细菌产生了抗药性，迫切需要新型抗菌剂。已经确定细菌细胞分裂蛋白的丝状温度敏感突变体Z（FtsZ）是有效且有前途的抗菌靶标。在这项研究中,通过早期识别能力评估最佳蛋白质，并使用Vina对加工过的化合物文库进行虚拟筛选。这一努力导致鉴定出14种潜在活性的抗微生物化合物。其中,化合物T5S1607对枯草芽孢杆菌ATCC9732(MIC=1μg/mL)和金黄色葡萄球菌ATC5C6538(MIC=4μg/mL)具有显著的抗菌效果。此外，体外实验表明，所选化合物T5S1607可快速杀死细菌并诱导FtsZ蛋白聚集，防止细菌分裂并导致细菌死亡。此外,细胞毒性和溶血实验表明,化合物T5S1607对LO2细胞表现出最小的毒性,并且在MIC浓度范围下在体外对哺乳动物细胞没有显著的溶血作用。所有结果表明化合物T5S1607是一种有前途的抗菌剂和潜在的FtsZ抑制剂。总之,这项工作通过虚拟筛选药物发现过程成功地发现了具有良好活性的FtsZ抑制剂。
