Yang Ping, Liu Hui-Zhong, Wang Ying-Si, Qi Hong, Wang Ling-Ling, Wang Bei-Bei, Xie Xiao-Bao
Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangdong Detection Centre of Microbiology Guangzhou 510070 China
RSC Med Chem. 2024 Feb 29;15(3):1003-1014. doi: 10.1039/d4md00017j. eCollection 2024 Mar 20.
Novel lead thiazole aminoguanidines exhibited strong activity against Gram-positive bacteria. The potential targets of these substances are undecaprenyl diphosphate synthase (UPPS) and undecaprenyl diphosphate phosphatase (UPPP). Here, we report the synthesis and antibacterial evaluation of a library of thiazole aminoguanidines analogues, wherein the rotatable bond is inserted between the C2 position of thiazole and hydrophobic group. The molecular flexibility is increased, and new analogues with strong activity against MRSA and are produced. The best compound 4i showed rapid sterilization and low tendency to induce bacterial resistance. The IC of compound 4i to EcUPPS enzyme is 145 μmol L (58 μg mL). Compound 4i can also inhibit and destroy bacterial biofilms. These thiazole aminoguanidines can be developed as potential therapeutic candidates in the future.
新型铅噻唑氨基胍对革兰氏阳性菌表现出强大的活性。这些物质的潜在靶点是十一异戊二烯二磷酸合酶（UPPS）和十一异戊二烯二磷酸磷酸酶（UPPP）。在此，我们报告了一系列噻唑氨基胍类似物的合成及抗菌评估，其中在噻唑的C2位与疏水基团之间插入了可旋转键。分子柔韧性增加，产生了对耐甲氧西林金黄色葡萄球菌（MRSA）具有强大活性的新类似物。最佳化合物4i显示出快速杀菌且诱导细菌耐药的倾向较低。化合物4i对大肠杆菌UPPS酶的IC50为145 μmol/L（58 μg/mL）。化合物4i还能抑制和破坏细菌生物膜。这些噻唑氨基胍未来可被开发为潜在的治疗候选药物。
