Bacterial infections continue to present a formidable challenge to human health, prompting intensified research efforts towards the development of effective antibacterial agents. This study harnesses click chemistry techniques to synthesize Isatin-1,2,3-triazole as a novel antibacterial agent, evaluating its in vitro efficacy against prevalent pathogens including Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) strains using both the microdilution and well-diffusion methods. The findings reveal a notable enhancement in antibacterial activity upon incorporation of the triazole moiety into the Isatin framework against both E. coli and S. aureus. Further analysis, including structure–activity relationship studies and molecular docking investigations, highlights the superior antibacterial potency of triazole-tethered Isatin tosyl azide compared to N-propargyl Isatin. Molecular docking simulations with Staphylococcus aureus (PDB ID: 4TU5) and Escherichia coli (PDB ID: 6YD9) proteins exhibit promising binding affinities of − 10.44 kJ/mol and − 8.4 kJ/mol, respectively. Isatin triazole demonstrates favorable gastrointestinal absorption properties, low toxicity profiles, adherence to Lipinski's rule of five, and compliance with Veber and Ghose standards. Furthermore, molecular dynamics simulations attest to the stability of protein complexes over a 100 ns timeframe. Collectively, these findings underscore the therapeutic potential of Isatin triazole compounds against bacterial infections, warranting further clinical exploration to elucidate their mechanisms of action and therapeutic efficacy.

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使用点击化学对含有 1,2,3-三唑的靛红支架进行合成、计算机内分子对接研究和体外抗菌评估

细菌感染继续对人类健康构成巨大挑战，促使人们加强研究工作，开发有效的抗菌剂。本研究利用点击化学技术合成 Isatin-1,2,3-三唑作为一种新型抗菌剂，并使用两种方法评估其对包括革兰氏阴性（大肠杆菌 ）和革兰氏阳性（金黄色葡萄球菌）菌株在内的常见病原体的体外功效。微量稀释法和充分扩散法。研究结果表明，将三唑部分掺入靛红框架后，对大肠杆菌和金黄色葡萄球菌的抗菌活性显着增强。进一步的分析，包括结构-活性关系研究和分子对接研究，强调了三唑系靛红甲苯磺酰叠氮化物与 N-炔丙基靛红相比具有优越的抗菌效力。金黄色葡萄球菌(PDB ID: 4TU5) 和大肠杆菌(PDB ID: 6YD9) 蛋白的分子对接模拟分别显示出 - 10.44 kJ/mol 和 - 8.4 kJ/mol 的良好结合亲和力。靛红三唑表现出良好的胃肠道吸收特性、低毒性、遵守 Lipinski 的五法则以及 Veber 和 Ghose 标准。此外，分子动力学模拟证明了蛋白质复合物在 100 ns 时间范围内的稳定性。总的来说，这些发现强调了靛红三唑化合物对抗细菌感染的治疗潜力，需要进一步的临床探索以阐明其作用机制和治疗功效。

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