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Spiropiperidyl rifabutins: expanded in vitro testing against ESKAPE pathogens and select bacterial biofilms

The Journal of Antibiotics volume 73, pages 868–872 (2020)Cite this article

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Abstract

The expanded microbiological evaluation of a series of rifastures, novel spiropiperidyl rifamycin derivatives, against clinically relevant ESKAPE bacteria has identified several analogs with promising in vitro bioactivities against antibiotic-resistant strains of Enterococcus faecium and Staphylococcus aureus. Thirteen of the rifastures displayed minimum inhibitory concentrations (MICs) below 1 µg/ml against the methicillin- and vancomycin-resistant forms of S. aureus and E. faecium (MRSA, VRSA, VRE). Aryl-substituted rifastures 1, 11, and 12 offered the greatest bioactivity, with MICs reaching ≤0.063 µg ml−1 for these human pathogens. Further analysis indicates that diphenyl rifasture 1 had greater antibiofilm activity against S. aureus and lower cytotoxicity in mammalian HEK cells than rifabutin.

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Acknowledgements

Financial support by Asturpharma S.A. and the projects PC-CIS01-22 (FICYT) and PR-01-GE-9 (Grupo de Excelencia FICYT) from the Consejería de Educación y Cultura del Principado de Asturias, and by Banco de Santander-Universidad de Oviedo (CEI “Ad Futurum” 10.01.633B.481.60) is gratefully acknowledged. This work was also supported in part by the National Institute of Allergy and Infectious Diseases, National Institutes of Health under award numbers AI151970 (T.E.L) and AI124458 (L.N.S.).

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Authors and Affiliations

  1. Departamento de Química Orgánica e Inorgánica, Instituto Universitario de Quimica Organometalica “Enrique Moles”, Universidad de Oviedo, C/ Julián Clavería, 8, 33006, Oviedo, Spain

    Marıa-Paz Cabal & Ana-Belén García

  2. Department of Pharmaceutical Science and Research, Marshall University School of Pharmacy, One John Marshall Drive, Huntington, WV, USA

    Timothy E. Long

  3. Department of Chemistry, University of South Florida, CHE 205, 4202 E. Fowler Avenue, Tampa, FL, USA

    Edward Turos

  4. Center for Drug Discovery and Innovation, University of South Florida, Tampa, FL, USA

    Edward Turos & Lindsey N. Shaw

  5. Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL, USA

    Jessie L. Allen, Bridget G. Budny & Lindsey N. Shaw

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  1. Marıa-Paz Cabal
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  2. Timothy E. Long
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  3. Edward Turos
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  4. Ana-Belén García
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  6. Bridget G. Budny
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  7. Lindsey N. Shaw
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Correspondence to Marıa-Paz Cabal.

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Cabal, MP., Long, T.E., Turos, E. et al. Spiropiperidyl rifabutins: expanded in vitro testing against ESKAPE pathogens and select bacterial biofilms. J Antibiot 73, 868–872 (2020). https://doi.org/10.1038/s41429-020-0346-x

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