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Design and Synthesis of Aza-β-Carboline Analogs and their Antibacterial Evaluation

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Pharmaceutical Chemistry Journal Aims and scope

Bacterial drug resistance has become a growing problem worldwide due to the excessive use of antibiotics in recent decades. Two small focused libraries of 5H-pyrimido[5,4-b]indole-4-carboxamides and 5H-pyrimido-[5,4-b]indole-4-ketones were designed as eudistomin Y3 and 1-acetyl-β-carboline (1-ABC) analogs and prepared via application of Inverse Electron-Demand Diels-Alder (IEDDA) reaction of 1,3,5-triazines and 3-aminoindoles. Compounds 2a and 2b were discovered to have activity against Mycobacterium bovis BCG with Minimum Inhibitory Concentration (MICs) values of 25 and 50 μg/mL respectively while compound 2e was against all three strains of Candida albicans tested with MIC values of 50 μg/mL. Moreover, compound 2e demonstrated synergistic antibacterial activity with fluconazol, which suggested that future drug candidates from this class of compounds could be used in combination with existing drugs to treat C. albicans infections.

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Acknowledgments

This work was supported by the Fundamental Research Funds of Jilin University (No. 45006050152), the Sci-Tech Development Projects of Jilin Province in China (No. 20140309010YY and No. 20180414075GH, and Changchun Discovery Sciences, Ltd.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Author notes

  1. Guoxing Xu and Qi Wei contributed equally.

Authors and Affiliations

  1. Center for Combinatorial Chemistry and Drug Discovery of Jilin University, School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin, 130021, P. R. China

    Guoxing Xu, Lihua Deng, Xiaoping Zhou, Qun Dang & Xu Bai

  2. Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, P. R. China

    Qi Wei, Fuhang Song, Huanqin Dai & Lixin Zhang

  3. College of Life Sciences, Hebei University, Baoding, 071002, P. R. China

    Qi Wei

  4. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, P. R. China

    Huanqin Dai & Lixin Zhang

Authors
  1. Guoxing Xu
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  2. Qi Wei
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  3. Fuhang Song
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  4. Huanqin Dai
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  5. Lihua Deng
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  6. Xiaoping Zhou
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  7. Lixin Zhang
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  8. Qun Dang
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  9. Xu Bai
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Corresponding authors

Correspondence to Lixin Zhang, Qun Dang or Xu Bai.

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Xu, G., Wei, Q., Song, F. et al. Design and Synthesis of Aza-β-Carboline Analogs and their Antibacterial Evaluation. Pharm Chem J 55, 365–372 (2021). https://doi.org/10.1007/s11094-021-02429-6

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  • DOI: https://doi.org/10.1007/s11094-021-02429-6

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