Bacterial DNA gyrase remains a prominent and vital target in discovering new antibacterial drugs. In the present research work, we designed and synthesized a series of novel 4,5-dibromo-N-phenyl-1H-pyrrole-2-carboxamide hybrids containing substituted 1,2,3-triazole and isoxazole moieties which could serve as potential E. coli DNA gyrase inhibitors. The title compounds were synthesized with a good to excellent yield, and all the newly synthesized compounds were characterized by physicochemical and spectral analysis (FTIR, ¹H NMR, and ¹³C NMR). The DNA gyrase (E. coli) inhibitory assay was performed for all synthesized compounds. Results showed that four compounds, 11a (IC₅₀ = 0.90 µM), 11b (IC₅₀ = 0.28 µM), 17a (IC₅₀ = 0.72 µM) and 17b (IC₅₀ = 0.43 µM), exhibited good DNA gyrase inhibitory activity. In-silico molecular docking study was performed to understand the mode of interaction of compounds with the target enzyme. A docking study on the E. coli DNA gyrase protein revealed that compounds 11b (-7.011 kcal/mol) and 17b (-6.60 kcal/mol) interact with ARG136 and ASP73, two key amino acid residues, with docking scores of −7.01 and −6.60, respectively. The MD simulation was further employed to elucidate the thermodynamic binding energy, RMSD, and RMSF of compounds 11b and 17b. They exhibited binding energies of -47.598 kcal/mol and -41.682 kcal/mol, respectively. This provides valuable information on the binding mode and structure-activity relationship of these new hybrids of 4,5-dibromo-N-phenyl-1H-pyrrole-2-carboxamides as promising E. coli DNA gyrase B inhibitors. In addition, these hybrid derivatives showed more prominent antibacterial action on Gram-negative rather than Gram-positive organisms. Surprisingly, compounds 11b (MIC = 1.56 µg/mL) and 17b (MIC = 3.125 µg/mL) also displayed promising anti-mycobacterial activity.

细菌DNA 旋转酶仍然是发现新抗菌药物的重要靶点。在目前的研究工作中，我们设计并合成了一系列含有取代的1,2,3-三唑和异恶唑部分的新型4,5-二溴-N-苯基-1H-吡咯-2-甲酰胺杂化物，可作为潜在的E . 大肠杆菌DNA 旋转酶抑制剂。标题化合物的合成具有良好至优异的产率，并且所有新合成的化合物均通过物理化学和光谱分析（FTIR、¹ H NMR 和¹³ C NMR）进行表征。对所有合成的化合物进行了DNA旋转酶（大肠杆菌）抑制测定。结果表明，四种化合物11a (IC ₅₀  = 0.90 µM)、11b (IC ₅₀  = 0.28 µM)、17a (IC ₅₀  = 0.72 µM) 和17b (IC ₅₀  = 0.43 µM) 表现出良好的DNA旋转酶抑制活性。进行了计算机分子对接研究，以了解化合物与目标酶的相互作用模式。对大肠杆菌DNA 旋转酶蛋白的对接研究表明，化合物11b (-7.011 kcal/mol) 和17b (-6.60 kcal/mol) 与两个关键氨基酸残基 ARG136 和 ASP73 相互作用，对接得分为 -7.01 和分别为-6.60。进一步采用MD模拟来阐明化合物11b和17b的热力学结合能、RMSD和RMSF 。它们的结合能分别为-47.598 kcal/mol和-41.682 kcal/mol。这为 4,5-二溴-N-苯基-1H-吡咯-2-甲酰胺的这些新杂合体作为有前景的大肠杆菌 DNA 旋转酶B 抑制剂的结合模式和构效关系提供了有价值的信息。此外，这些杂种衍生物对革兰氏阴性菌比革兰氏阳性菌表现出更显着的抗菌作用。令人惊讶的是，化合物11b (MIC = 1.56 µg/mL) 和17b (MIC = 3.125 µg/mL) 也表现出有希望的抗分枝杆菌活性。