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Synergistic action of substituted indole derivatives and clinically used antibiotics against drug-resistant bacteria

Departments of Chemistry and Biology, New Mexico Tech, 801 Leroy Place, Socorro, NM 87801, USA

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Leslie Edwards

Departments of Chemistry and Biology, New Mexico Tech, 801 Leroy Place, Socorro, NM 87801, USA

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Alexander Kornienko

https://orcid.org/0000-0003-2041-7367

Departments of Chemistry and Biology, New Mexico Tech, 801 Leroy Place, Socorro, NM 87801, USA

Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX 78666, USA

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Liliya V Frolova

Departments of Chemistry and Biology, New Mexico Tech, 801 Leroy Place, Socorro, NM 87801, USA

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Snezna Rogelj

*Author for correspondence:

E-mail Address: snezna.rogelj@nmt.edu

Departments of Chemistry and Biology, New Mexico Tech, 801 Leroy Place, Socorro, NM 87801, USA

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Published Online:2 Jun 2020https://doi.org/10.2217/fmb-2019-0094

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Abstract

Aim: The current report describes the discovery of indole derivatives that synergize with standard antibiotics. Materials & methods: The antibacterial activities were determined using an optimized time–kill method, while viability of mammalian cells was assessed using the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Results: The synergy is observed with methicillin- and vancomycin-resistant Staphylococcus aureus bacterial strains, against which the standard antibiotics show no activities of their own. Our indole derivatives in combination with antibiotics lack toxicity toward mammalian cells, do not promote the evolution of resistance of S. aureus in comparison to clinically established antibiotics, and likely work by permeabilizing bacterial cell membranes. Conclusion: The above-mentioned findings demonstrate the potential clinical applications of our indole derivatives.

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Vol. 15, No. 8

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History

Received 29 March 2019

Accepted 9 April 2020

Published online 2 June 2020

Published in print May 2020

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Keywords

Author contributions

DN Turner, L Edwards and LV Frolova performed the experiments. A Kornienko designed the study and wrote the manuscript. S Rogelj designed the study and oversaw the laboratory work.

Acknowledgments

S Rogelj and LV Frolova acknowledge their NMT Presidential Research Support.

Financial & competing interests disclosure

This project was supported by a grant from the National Institute of General Medical Sciences (P20GM103451). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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