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Chinese Journal of Organic Chemistry >

2024 , Vol. 44 >Issue 1: 204 - 215

DOI: https://doi.org/10.6023/cjoc202307018

ARTICLES

Novel γ-Carboline Derivatives as Antibacterial Agents: Synthesis and Antibacterial Evaluation

  • Haibo Huo ,
  • Guixia Li ,
  • Shijun Wang ,
  • Chun Han ,
  • Baojun Shi ,
  • Jian Li
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  • a Department of Life Sciences, Changzhi University, Changzhi, Shanxi 046011
    b Department of Basic Medicine, Changzhi Medical College, Changzhi, Shanxi 046011
    c Department of Chemistry, Changzhi University, Changzhi, Shanxi 046011
    d College of Plant Protection, Northwest A&F University, Yangling, Shaanxi 712100
†The authors contributed equally to this work.
*E-mail:

Received date: 2023-07-17

  Revised date: 2023-08-31

  Online published: 2023-09-15

Supported by

National Natural Science Foundation of China(82204247); National Natural Science Foundation of Shanxi Province(202103021223378); National Natural Science Foundation of Shanxi Province(202103021223382); the National Natural Science Foundation of Shanxi Province(202203021212168); Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi Province(2022L510)

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Abstract

Forty-five novel 8-methoxyl-γ-carboline derivatives were designed and effectively synthesized with commercially available starting materials, 4-methoxyphenylhydrazine hydrochloride 7 and piperidone 8, via Fischer indole synthesis process to prepare key intermediate 9, which underwent oxidation, acylation or alkylation to yield the target derivatives. The antibacterial activities of all compounds were evaluated against Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa) and Ralstonia solanacearum (R. solanacearum). The results indicated that (8-methoxy-5H- pyrido[4,3-b]indol-5-yl)(4-methoxyphenyl)methanone (11g), furan-2-yl(8-methoxy-5H-pyrido[4,3-b]indol-5-yl)methanone (11n), 5-(2-bromobenzyl)-8-methoxy-5H-pyrido[4,3-b]indole (12f), 5-(3-bromobenzyl)-8-methoxy-5H-pyrido[4,3-b]indole (12g), 8-methoxy-5-(4-(trifluoromethoxy)benzyl)-5H-pyrido[4,3-b]indole (12h) and 2-(4-chlorobenzyl)-8-methoxy-5H-pyri- do[4,3-b]indol-2-ium bromide (13e) showed a broad spectrum of antibacterial activity. Especially compounds 12f and 12h exhibited comparable antibacterial activity with the positive control (ampicillin sodium) with minimum inhibitory concentration (MIC) value of 8 μg/mL. Moreover, membrane-active mechanism was studied further via fluorescent microscopy, which suggested that derivative 12h exerted its antibacterial effect by damaging the membranes of the bacteria. Some structure-activity relationships among the forty-five derivatives are discussed and several important determinants for the activity of these compounds are identified. This work offers useful instructions for the development of new antibiotics.

Key words： 8-methoxyl-N2 &; N5-substituted γ-carbolines; antibacterial activity; structure-activity relationships; mechanism

Cite this article

Haibo Huo , Guixia Li , Shijun Wang , Chun Han , Baojun Shi , Jian Li . Novel γ-Carboline Derivatives as Antibacterial Agents: Synthesis and Antibacterial Evaluation[J]. Chinese Journal of Organic Chemistry, 2024 , 44(1) : 204 -215 . DOI: 10.6023/cjoc202307018

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