Abstract Tuberculosis (TB) is an infectious disease and caused by various strains of mycobacteria. In the present study, pharmacophore model was developed using single ligand by ligand-based drug discovery approach. The key features responsible for DprE1 inhibitory activity were taken into consideration for developing pharmacophore. After the virtual screening, top 1000 hits were further subjected to docking study using GLIDE module, Schrödinger. Docking studies have shown promising interaction with amino residues with better glide score. Ligand-based drug design approach yielded a series of 15, 2-(6-nitrobenzo[d]thiazol-2-ylthio)-N-benzyl-N-(6-nitrobenzo[d]thiazol-2-yl)acetamide derivatives. All synthesized derivatives were characterized using NMR, mass, CHN analysis. The synthesized compounds were screened for In vitro antitubercular activity against Mycobacterium tuberculosis (H37Rv). Four compounds, 5g (MIC-1.01 μM); 5i (MIC-0.91 μM); 5k (MIC-0.82 μM); and 5o (MIC-1.04 μM) has shown promising activity compared to MIC of standard isoniazid (INH) and DprE1 enzyme inhibition was compared to BTZ043. Two halogen-substituted compounds have exhibited drastic enzyme inhibition. GRAPHICAL ABSTRACT

中文翻译：

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一些 2-(6-硝基苯并[d]噻唑-2-基硫基)-N-苄基-N-(6-硝基苯并[d]噻唑-2-基)乙酰胺衍生物作为选择性 DprE1 抑制剂的设计、合成和生物学评价

摘要 结核病（TB）是一种由多种分枝杆菌引起的传染病。在本研究中，药效团模型是通过基于配体的药物发现方法使用单个配体开发的。开发药效团时考虑了负责 DprE1 抑制活性的关键特征。在虚拟筛选之后，使用 GLIDE 模块 Schrödinger 进一步对前 1000 个匹配项进行对接研究。对接研究表明，与具有更好滑行评分的氨基残基的相互作用很有希望。基于配体的药物设计方法产生了一系列 15, 2-(6-nitrobenzo[d]thiazol-2-ylthio)-N-benzyl-N-(6-nitrobenzo[d]thiazol-2-yl)acetamide 衍生物。使用NMR、质量、CHN分析表征所有合成的衍生物。筛选合成的化合物对结核分枝杆菌 (H37Rv) 的体外抗结核活性。四种化合物，5g (MIC-1.01 μM)；5i (MIC-0.91 μM)；5k (MIC-0.82 μM)；和 5o (MIC-1.04 μM) 与标准异烟肼 (INH) 的 MIC 相比显示出有希望的活性，并将 DprE1 酶抑制与 BTZ043 进行比较。两种卤素取代的化合物表现出强烈的酶抑制作用。图形概要