The increasing incidence of multidrug resistant bacterial infection renders an urgent need for the development of new antibiotics. To develop small molecules disturbing FtsZ activity has been recognized as promising approach to search for antibacterial of high potency systematically. Herein, a series of novel quinolinium derivatives were synthesized and their antibacterial activities were investigated. The compounds show strong antibacterial activities against different bacteria strains including MRSA, VRE and NDM-1 Escherichia coli. Among these derivatives, a compound bearing a 4-fluorophenyl group (A2) exhibited a superior antibacterial activity and its MICs to the drug-resistant strains are found lower than those of methicillin and vancomycin. The biological results suggest that these quinolinium derivatives can disrupt the GTPase activity and dynamic assembly of FtsZ, and thus inhibit bacterial cell division and then cause bacterial cell death. These compounds deserve further evaluation for the development of new antibacterial agents targeting FtsZ.

中文翻译：

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3-甲基苯并[d]噻唑-甲基喹啉鎓衍生物的抗菌活性及其作用机理的研究。

耐多药细菌感染的发生率不断增加，迫切需要开发新的抗生素。开发干扰FtsZ活性的小分子已被公认为是系统地寻找高效抗菌素的有前途的方法。在此，合成了一系列新颖的喹啉鎓衍生物，并研究了它们的抗菌活性。该化合物对包括MRSA，VRE和NDM-1大肠杆菌在内的不同细菌菌株显示出强大的抗菌活性。在这些衍生物中，带有4-氟苯基的化合物（A2）显示出优异的抗菌活性，并且发现其对耐药菌株的MIC低于甲氧西林和万古霉素。生物学结果表明，这些喹啉鎓衍生物可以破坏GTPase活性和FtsZ的动态装配，从而抑制细菌细胞分裂，进而引起细菌细胞死亡。这些化合物值得进一步评估，以开发针对FtsZ的新型抗菌剂。