2-(1-吲哚-3-基)-1-苯并[]咪唑衍生物的合成、抗菌和抗生物膜活性及分子对接研究。

Synthesis, Antimicrobial and Antibiofilm Activities, and Molecular Docking Investigations of 2-(1-Indol-3-yl)-1-benzo[]imidazole Derivatives.

机构信息

Department of Chemistry, Perm State University, Bukireva St. 15, 614990 Perm, Russia.

Department of Biology, Perm State University, Bukireva St. 15, 614990 Perm, Russia.

出版信息

Molecules. 2023 Oct 14;28(20):7095. doi: 10.3390/molecules28207095.

DOI:10.3390/molecules28207095

PMID:37894573

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10609029/

Abstract

The treatment of many bacterial and fungal infections remains a problem due to increasing antibiotic resistance and biofilm formation by pathogens. In the present article, a methodology for the chemoselective synthesis of 2-(1-indol-3-yl)-1-benzo[]imidazole derivatives is presented. We report on the antimicrobial activity of synthesized 2-(1-indol-3-yl)-1-benzo[]imidazoles with significant activity against ATCC 25923, ATCC 43300 (MRSA), (mc(2)155/ATCC 700084), and ATCC 10231. High activity against staphylococci was shown by indolylbenzo[]imidazoles and (minimum inhibitory concentration (MIC) < 1 µg/mL) and and (MIC 3.9-7.8 µg/mL). A low MIC was demonstrated by 2-(1-indol-3-yl)-1-methyl-1-benzo[]imidazole () against and against (3.9 µg/mL and 3.9 µg/mL, respectively). 2-(5-Bromo-1-indol-3-yl)-6,7-dimethyl-1-benzo[]imidazole () showed a low MIC of 3.9 µg/mL against . Compounds , , , and exhibited excellent antibiofilm activity, inhibiting biofilm formation and killing cells in mature biofilms. Molecular docking analysis identified three potential interaction models for the investigated compounds, implicating (p)ppGpp synthetases/hydrolases, FtsZ proteins, or pyruvate kinases in their antibacterial action mechanism.

摘要

由于病原体对抗生素的耐药性增加和生物膜的形成，许多细菌和真菌感染的治疗仍然是一个问题。在本文中，提出了一种化学选择性合成 2-(1-吲哚-3-基)-1-苯并[]咪唑衍生物的方法。我们报告了合成的 2-(1-吲哚-3-基)-1-苯并[]咪唑的抗菌活性，它们对 ATCC 25923、ATCC 43300（MRSA）、（mc(2)155/ATCC 700084）和 ATCC 10231 具有显著的活性。具有吲哚基苯并[]咪唑的化合物和（最低抑菌浓度 (MIC) < 1 µg/mL）和（MIC 3.9-7.8 µg/mL）对葡萄球菌表现出高活性。2-(1-吲哚-3-基)-1-甲基-1-苯并[]咪唑 () 对和（MIC 分别为 3.9 µg/mL 和 3.9 µg/mL）的 MIC 较低。2-(5-溴-1-吲哚-3-基)-6,7-二甲基-1-苯并[]咪唑 () 对显示出较低的 MIC（3.9 µg/mL）。化合物、、、和表现出优异的抗生物膜活性，抑制生物膜形成并杀死成熟生物膜中的细胞。分子对接分析确定了三种潜在的相互作用模型，涉及（p）ppGpp 合酶/水解酶、FtsZ 蛋白或丙酮酸激酶在其抗菌作用机制中的作用。