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Novel Quinoxaline Derivatives: Design, Synthesis, Bioactive Evaluation, SARs, and Preliminary Antibacterial Mechanism

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Abstract

A novel series of quinoxaline derivatives (IVa–IVn) have been designed and synthesized to evaluate their antibacterial activity, structure-activity relationships (SARs), antibacterial mechanism and in vivo antibacterial efficacy. Compound (IVk) displayed excellent antibacterial activity with MIC values of 4 μg/mL against Gram-positive and 16–32 μg/mL against Gram-negative bacteria. Further tests against drug-resistant bacteria showed (IVk) exhibited good antibacterial activity against MRSA and K. pneumonia with MIC values of 4–16 μg/mL. Compound (IVk) also demonstrated a lower tendency for developing bacterial resistance compared to the positive controls. Furthermore, this active molecule (IVk) showed strong bactericidal activity against MRSA at 3 MIC (>7 log10 CFU mL–1 reduction) after 7 h, whereas the positive control group only demonstrated inhibitory activity. The study of cytotoxicity and mechanism revealed that (IVk) not only had minimal cytotoxicity, but also could rapidly inhibit the growth of bacteria by impairing the integrity of cell membranes. Preliminary in vivo results confirmed that (IVk) (2.5 mg/mL) could reduce the survival rate of bacteria by 31% after five days of continuous treatment, and by 75% when the concentration was increased to 5.0 mg/mL. These results indicate that (IVk) may have potential drug properties and deserve further attention and study.

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DATA AVAILABILITY

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This work was supported by Science and technology research project of Chongqing education commission (grant no. KJQN201902715).

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Authors and Affiliations

  1. Chongqing Three Gorges Medical College, 404020, Chongqing, China

    Zhongde Xie & Liqing Wang

  2. ffiliated People’s Hospital of Chongqing Three Gorges Medical College, 404020, Chongqing, China

    Xuelian Dai

Authors
  1. Zhongde Xie
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  2. Xuelian Dai
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  3. Liqing Wang
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Contributions

The authors LW and ZX designed the experiments. The authors ZX and XD synthesized the derivatives and carried out their NMR analysis. The authors ZX and XD completed pharmacological analysis and data processing. The authors LW, ZX, and XD contributed to manuscript preparation.

All authors participated in the discussions.

Corresponding author

Correspondence to Liqing Wang.

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This article does not contain any studies involving patients or animals as test objects. Informed consent was not required for this article. No conflict of interest was declared by the authors.

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Xie, Z., Dai, X. & Wang, L. Novel Quinoxaline Derivatives: Design, Synthesis, Bioactive Evaluation, SARs, and Preliminary Antibacterial Mechanism. Russ J Bioorg Chem 49 (Suppl 1), S132–S145 (2023). https://doi.org/10.1134/S1068162023080113

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  • DOI: https://doi.org/10.1134/S1068162023080113

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