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Letters in Drug Design & Discovery

Author(s): Shuchen Pei, Jinhua Yang, Shihao Xia, Shuting Tang, Kangyao Yuan and Jun Chen*

DOI: 10.2174/1570180819666220317151208

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Design, Synthesis, and Anti-Bacterial Evaluation of Tetrahydrobenzothiophene Derivatives as Lipopolysaccharide Biogenesis Inhibitors

Page: [335 - 342] Pages: 8

  • * (Excluding Mailing and Handling)

Abstract

Background: Bacterial infections caused by multidrug-resistant bacteria have emerged as major threats to human communities worldwide. There is a great need to develop new mechanisms by which anti-bacterial agents can combat bacterial antibiotic resistance.

Objective: This study aims to synthesize and characterize a series of novel tetrahydrobenzothiophene derivatives and evaluate their anti-bacterial activities.

Methods: In this study, we have synthesized 2-benzamido-4,5,6,7-tetrahydrobenzo[b]thiophene-3- carboxylic acid derivatives (3a-3r) and investigated their anti-bacterial activities against E. coli, P. aeruginosa, Salmonella, and S. aureus.

Results: The MIC values demonstrated that all synthesized derivatives possessed potent anti-bacterial activity properties. Compounds 3b, 3e, 3f, 3g, 3h, 3n, and 3q exhibited in vitro excellent anti-bacterial efficiency. Compounds 3b, 3e, 3f, and 3p were evaluated by in vitro time-kill assay; they displayed concentration- dependent bacteriostatic effects. Compounds 3b, 3e, 3f, and 3p showed moderate water solubility, high stability in plasma, and moderate acute oral toxicity.

Conclusion: Most of the 2-benzamido-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid derivatives exhibited potent anti-bacterial activities. The data reported in this paper may guide the design of tetrahydrobenzothiophene derivatives.

Keywords: Tetrahydrobenzothiophene, lipopolysaccharide biogenesis inhibitors, synthesis, design, anti-bacterial activity, ADME.

Graphical Abstract

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