3-芳基取代的咪唑并[1,2-a]吡啶类化合物作为抗结核药物。
3-Aryl-substituted imidazo[1,2-a]pyridines as antituberculosis agents.
机构信息
Department of Organic Synthesis and Process Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
Academy of Scientific and Innovative Research, Ghaziabad, Uttar Pradesh, India.
出版信息
Arch Pharm (Weinheim). 2021 Oct;354(10):e2000419. doi: 10.1002/ardp.202000419. Epub 2021 Jun 29.
Novel inhibitors are needed to tackle tuberculosis. Herein, we report the 3-aryl-substituted imidazo[1,2-a]pyridines as potent antituberculosis agents. A small library of 3-aryl-substituted imidazo[1,2-a]pyridines was synthesized using direct arylation, followed by nitro reduction and finally Pd-catalyzed C-N coupling reactions. The compounds thus obtained were evaluated against Mycobacterium tuberculosis H37Rv. Compound 26 was identified as an antituberculosis lead with a minimum inhibitory concentration of 2.3 μg/ml against M. tuberculosis H37Rv. This compound showed a selectivity index of 35. The docking of 26 in the active site of the M. tuberculosis cytochrome bc1 complex cytochrome b subunit (Mtb QcrB) revealed key π-π interactions of compound 26 with the Tyr389 and Trp312 residues of Mtb QcrB.
需要新型抑制剂来应对结核病。在此，我们报告了 3-芳基取代的咪唑并[1,2-a]吡啶作为有效的抗结核药物。使用直接芳基化、硝基还原和最后钯催化的 C-N 偶联反应合成了 3-芳基取代的咪唑并[1,2-a]吡啶的小库。由此得到的化合物针对结核分枝杆菌 H37Rv 进行了评估。化合物 26 被鉴定为具有抗结核作用的先导化合物，对 M. tuberculosis H37Rv 的最小抑菌浓度为 2.3μg/ml。该化合物的选择性指数为 35。化合物 26 在结核分枝杆菌细胞色素 bc1 复合物细胞色素 b 亚基（Mtb QcrB）的活性部位的对接揭示了化合物 26 与 Mtb QcrB 的 Tyr389 和 Trp312 残基的关键 π-π 相互作用。
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