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Synergistic antimicrobial and antibiofilm activities of piperic acid and 4-ethylpiperic acid amides in combination with ciprofloxacin

The Journal of Antibiotics volume 75, pages 236–242 (2022)Cite this article

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Abstract

In the present work, piperic acid and 4-ethylpiperic acid (EPA) amides with amino acids (C1–C8) were bio-evaluated for their antimicrobial activity and biofilm inhibition against Gram-positive and Gram-negative bacterial strains. Among all, EPA-β3,3-Pip(Bzl)-OMe, C2 displayed the potent antimicrobial activity with MIC of 6.25 μg ml–1 against Gram-negative bacteria Escherichia coli. In combination studies, the FIC indices suggested that C1 and C2 have a synergistic effect with ciprofloxacin against E. coli and Bacillus subtilis, whereas C5 exhibited a synergistic effect with ciprofloxacin against all the tested bacteria. The inhibitory effect of amides C1, C2, and C5 on the biofilm formation of test strains was significantly potentiated by co-administration with ciprofloxacin. Furthermore, the effective concentrations of C2 in combination reduced drastically compared to alone for biofilm inhibition. At these concentrations, C2 showed negligible hemolytic and cytotoxic activities.

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Acknowledgements

We acknowledge the Council of Scientific and Industrial Research (CSIR), New Delhi, and ICAR, India, for financial assistance under Network Project BSC-120 and GAP2123. We also acknowledge Dr Surrinder Koul for providing 4-ethylpiperic acid. GS is thankful to the Indian Council of Medical Research, while NAW, SS, and JR are thankful to the Council of Scientific and Industrial Research (CSIR), for providing research fellowship. The manuscript bears IIIM Communication No. CSIR-IIIM/IPR/00360.

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  1. These authors contributed equally: Gurpreet Singh, Naiem Ahmad Wani

Authors and Affiliations

  1. Microbial Biotechnology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu-Tawi, 180001, India

    Gurpreet Singh & Meenu Katoch

  2. Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India

    Gurpreet Singh, Naiem Ahmad Wani, Junaid Ur Rahim, Sudha Shankar, Rajkishor Rai & Meenu Katoch

  3. Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu-Tawi, 180001, India

    Naiem Ahmad Wani, Junaid Ur Rahim, Sudha Shankar & Rajkishor Rai

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  1. Gurpreet Singh
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Contributions

NW, JR, SS provided the amides of PA and EPA, which were synthesized under the supervision of RR. MK designed the study. GS did the experimentation and MK analyzed the data. GS and MK wrote the paper, and MK and RR reviewed and edited the manuscript.

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Correspondence to Rajkishor Rai or Meenu Katoch.

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Singh, G., Wani, N.A., Rahim, J.U. et al. Synergistic antimicrobial and antibiofilm activities of piperic acid and 4-ethylpiperic acid amides in combination with ciprofloxacin. J Antibiot 75, 236–242 (2022). https://doi.org/10.1038/s41429-022-00508-8

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