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Benzothiophene Schiff Bases Disrupt Cytoplasmic Membrane Integrity of Gram-Positive and -Negative Bacteria Cells

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Abstract

Objective: With the molecular formula C8H6S, benzothiophene is an appealing synthon showing a wide range of biological activities such as antifungal, antibacterial, antitumor and anticancer properties. Due to increasing concern about the resistance gained by the microorganisms against existing antimicrobial agents, our group is interested in revealing the cellular target site of these compounds. Methods: As a part of our efforts on determination of effect of antibacterial agents, in this study, we focused on the benzothiophene Schiff bases. Antibacterial activity of bis(benzo[b]thiophene-2-yl)alkylmethanimine derivatives was studied via minimum inhibitory concentration measurements. Results and Discussion: One of the compounds, compound (I) (N,N′-(propane-1,3-diyl)bis(1-(benzo[b]thiophene-2-yl))methanimine), proved to be highly active against both Gram-positives; Staphylococcus aureus, Bacillus subtilis, Enterococcus faecalis, Bacillus cereus; and Gram-negatives Escherichia coli, Pseudomonas aeruginosa, Salmonella enteritidis, Shigella flexneri. In order to reveal the effect of this compound on bacterial cytoplasmic membrane, we measured the extracellular conductivity increase upon treatment. Compound (I), showing high antibacterial activity caused a sudden increase of extracellular conductivity due to ion leakage from bacterial cells. In contrast, inactive benzothiophene derivatives did not cause any conductivity increase. Conclusions: We propose that benzothiophene Schiff base (I) disrupts bacteria cytoplasmic membrane integrity, and this action contributes to its antibacterial activity.

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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 regular institutional funding, and no additional grants were obtained.

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Authors and Affiliations

  1. Department of Bioengineering, Gebze Technical University, 41400, Kocaeli, Turkey

    Bengü Ergüden & Hatice Büşra Lüleci

  2. Department of Chemistry, Faculty of Sciences, Karadeniz Technical University, 61080, Trabzon, Turkey

    Yasemin Ünver

Authors
  1. Bengü Ergüden
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  2. Hatice Büşra Lüleci
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  3. Yasemin Ünver
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Contributions

The author YÜ synthesized compounds (I) and (II); the authors HBL and BE designed and performed the experiments. The authors YÜ, HBL, and BE wrote the manuscript.

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Correspondence to Bengü Ergüden.

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Ergüden, B., Lüleci, H.B. & Ünver, Y. Benzothiophene Schiff Bases Disrupt Cytoplasmic Membrane Integrity of Gram-Positive and -Negative Bacteria Cells. Russ J Bioorg Chem 50, 128–137 (2024). https://doi.org/10.1134/S1068162024010096

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