Background: The rapid evolution of antibiotic resistance poses a serious threat to public health. The development of heterocyclic benzothiazole derivatives, as efficient and potential agents, has been the focus of antibacterial drug discovery.

Objective: Present study attempts to evaluate the antibacterial activity and mechanism of action of novel 2-(4’- aminophenyl) benzothiazole derivatives.

Methods: Antibacterial activity of novel benzothiazole derivatives was evaluated by agar disc diffusion method against a panel of susceptible Gram-positive and Gram-negative strains. The mechanism of action was explored by bactericidal kinetics, membrane depolarization, fluorescent assisted cell cytometry and DNA cleavage studies.

Results: Our findings revealed that compounds A07a and A07b turned out to be the most potent analogues having minimum inhibitory concentration values in the range of 3.91-31.2 µg/ml against Staphylococcus aureus, Salmonella typhi, Pseudomonas aeruginosa and Escherichia coli. The new benzothiazole derivatives displayed different modes of action as elucidated by the studies on intact bacterial cells and plasmid DNA. The structure activity relationship studies showed prominent activity of compound A07a containing oxime moiety on carbonyl carbon along with less bulky electron releasing and lipophillic group (methoxy and chloro) in phenyl ring at C2 position of 2-(4’-aminophenyl) benzothiazole ring system.

Conclusion: The potent antibacterial activity of compounds (A07a and A07b) was mediated by membrane perturbing and intracellular mode of actions. These results further validate the use of these derivatives in the treatment of microbial diseases and provide scope for further research.

背景：抗生素耐药性的迅速发展对公共健康构成了严重威胁。作为有效和潜在试剂的杂环苯并噻唑衍生物的开发一直是抗菌药物发现的重点。

目的：本研究试图评估新型2-（4'-氨基苯基）苯并噻唑衍生物的抗菌活性和作用机理。

方法：通过琼脂圆盘扩散法评估新型苯并噻唑衍生物对一组敏感的革兰氏阳性和革兰氏阴性菌株的抗菌活性。通过杀菌动力学，膜去极化，荧光辅助细胞流式细胞术和DNA裂解研究探索了作用机理。

结果：我们的发现表明，化合物A07a和A07b是最有效的类似物，对金黄色葡萄球菌，伤寒沙门氏菌，铜绿假单胞菌和大肠杆菌的最小抑菌浓度值在3.91-31.2 µg / ml范围内。如对完整细菌细胞和质粒DNA的研究所阐明的那样，新的苯并噻唑衍生物显示出不同的作用方式。结构活性关系研究表明，含肟部分的化合物A07a在羰基碳上具有显着活性，同时在2-（4'-氨基苯基）苯并噻唑环系统C2位的苯环中具有较小的电子释放和亲脂性基团（甲氧基和氯）。

结论：化合物（A07a和A07b）的有效抗菌活性是通过膜干扰和细胞内作用方式介导的。这些结果进一步证实了这些衍生物在微生物疾病治疗中的用途，并提供了进一步研究的范围。