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1,4-Dihydropyridine Cationic Peptidomimetics with Antibacterial Activity

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Abstract

We synthesized new broad spectrum antibacterial cationic peptidomimetics centered on a hydrophobic 1,4-dihydropyridine (1,4-DHP) scaffold. The synthesis involves the preparation of the scaffold in a three step Hantzsch reaction followed by simultaneous coupling of the 1,4-DHP scaffold to two dipeptides bearing cationic side chains. The synthesized peptidomimetics were found to have no measurable toxic hemolytic effect against mammalian red blood cells. The compounds were found to have antibacterial activity against Gram-(−) and Gram-(+) bacteria with MICs in the range of 35–100 μg/mL. These cationic antimicrobial peptidomimetics will lead to more effective antibacterial drug candidates based on a synthetically accessible scaffold.

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Abbreviations

1,4-DHP:

1,4-dihydropyridine

BDZP:

Benzodiazepine

HOBt:

N-hydroxyl benzotriazole

MIC:

Minimal inhibitory concentration

RBC:

Red blood cells

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Acknowledgments

The authors thank Dr. Hugo Gottlieb from Bar-Ilan University for NMR experiments and helpful advice. We also thank Dr. Galina M. Zats for compounds 11 and 12. This work was supported by the Authority for Research & Development of Ariel University.

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Authors and Affiliations

  1. Department of Chemistry, Bar-Ilan University, Ramat Gan, Israel

    Inbal Lapidot & Amnon Albeck

  2. Department of Biological Chemistry, Ariel University, Ariel, Israel

    Inbal Lapidot, Gary Gellerman, Shimon Shatzmiller & Flavio Grynszpan

Authors
  1. Inbal Lapidot
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  2. Amnon Albeck
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  3. Gary Gellerman
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  4. Shimon Shatzmiller
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  5. Flavio Grynszpan
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Corresponding authors

Correspondence to Shimon Shatzmiller or Flavio Grynszpan.

Electronic Supplementary Material

Supplementary data (synthetic details, selected MS, 1H and 13C NMR spectra) associated with this work can be found in the online version at doi:

Supplementary material 1 (DOC 221 kb)

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Lapidot, I., Albeck, A., Gellerman, G. et al. 1,4-Dihydropyridine Cationic Peptidomimetics with Antibacterial Activity. Int J Pept Res Ther 21, 243–247 (2015). https://doi.org/10.1007/s10989-015-9460-1

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  • DOI: https://doi.org/10.1007/s10989-015-9460-1

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