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Synergistic antimicrobial activity of N-methyl substituted pyrrolidinium–based ionic liquids and melittin against Gram-positive and Gram-negative bacteria

  • Biotechnological products and process engineering
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Abstract

In pharmaceutical industry, the prodrug approaches and drug-drug conjugates are being now vastly used to optimize the efficacy of the drugs for multipurpose. The combination or conjugation of antimicrobials agents with natural antimicrobials may lead to better synergistic antimicrobial activity. Currently, many publications show the potential of ionic liquids (ILs) as novel antimicrobials and even as active pharmaceutical ingredients. The current study showed the synthesis of novel pyrrolidinium-based ILs (Cx, x = 4, 6, 8, 10, 12) and their antibacterial activity alone and in combination with antimicrobial peptide, melittin (MEL), against clinically relevant microorganism, E. coli and S. aureus. The cytotoxicity of synthesized ILs was administered on HEK 293 cell line using MTT assay. The obtained results showed the dependency of antibacterial activity of ILs on alkyl chain length (C4 < C6 < C8 < C10 < C12). The remarkable improvement in the antibacterial efficiency of MEL was seen with ILs; however, antibacterial effect is more pronounced with IL having large alkyl chain length (C8, C10, and C12) at their minimal concentration with MEL to disrupt the cell membrane. In addition, the binding study and haemocompatibility results showed favourable biocompatibility and stability which could potentially improve its utility for the biomedical field.

Key points

• The combination of melittin and pyrrolidinium-based ILs showed improved antibacterial activity against E. coli and S. aureus which may be used for developing new antibacterial agents.

• Moreover, the cytotoxicity and haemocompatibility results showed excellent biocompatibility of the combinations on human cell line and human serum albumin, respectively, which could potentially improve its utility for the biomedical field.

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Acknowledgements

This research was supported by the Researchers Supporting Project number (RSP-2020/35), King Saud University, Riyadh, Saudi Arabia. Dr. Rajan Patel greatly acknowledges the financial support from the Science and Engineering Research Board (EEQ/2016/000339) New Delhi, India. Juhi Saraswat is also thankful to the ICMR, New Delhi, India, for providing a research grant (F. No.45/19/2019-BIO/BMS).

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Authors and Affiliations

  1. Biophysical Chemistry Laboratory, Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India

    Juhi Saraswat & Rajan Patel

  2. Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia

    Badr Aldahmash

  3. Doping Research Chair, Department of Zoology, College of Science, King Saud University, Riyadh, 11451, Kingdom of Saudi Arabia

    Suliman Yousef AlOmar

  4. Department of Bioscience, Jamia Millia Islamia, New Delhi, 110025, India

    Khalid Imtiyaz & M. Moshahid Alam Rizvi

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  1. Juhi Saraswat
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  2. Badr Aldahmash
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  3. Suliman Yousef AlOmar
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  4. Khalid Imtiyaz
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  5. M. Moshahid Alam Rizvi
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  6. Rajan Patel
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Contributions

JS performed the whole experimental part and wrote the manuscript.

KI performed the cytotoxicity experiment in the study.

MA wrote the cytotoxicity part in the manuscript.

SYA and BA help to revise the manuscript.

RP is the corresponding author.

Corresponding author

Correspondence to Rajan Patel.

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The authors declare that they have no conflict of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Supplementary Information

1H NMR, 13C NMR, FT-IR and Mass spectra of ILs, Fluorescence spectroscopy, Surface tension measurement.

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Saraswat, J., Aldahmash, B., AlOmar, S.Y. et al. Synergistic antimicrobial activity of N-methyl substituted pyrrolidinium–based ionic liquids and melittin against Gram-positive and Gram-negative bacteria. Appl Microbiol Biotechnol 104, 10465–10479 (2020). https://doi.org/10.1007/s00253-020-10989-y

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  • DOI: https://doi.org/10.1007/s00253-020-10989-y

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