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Polyhydroxyalkanoate-based 3-hydroxyoctanoic acid and its derivatives as a platform of bioactive compounds

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Abstract

A library of 18 different compounds was synthesized starting from (R)-3-hydroxyoctanoic acid which is derived from the bacterial polymer polyhydroxyalkanoate (PHA). Ten derivatives, including halo and unsaturated methyl and benzyl esters, were synthesized and characterized for the first time. Given that (R)-3-hydroxyalkanoic acids are known to have biological activity, the new compounds were evaluated for antimicrobial activity and in vitro antiproliferative effect with mammalian cell lines. The presence of the carboxylic group was essential for the antimicrobial activity, with minimal inhibitory concentrations against a panel of bacteria (Gram-positive and Gram-negative) and fungi (Candida albicans and Microsporum gypseum) in the range 2.8–7.0 mM and 0.1–6.3 mM, respectively. 3-Halogenated octanoic acids exhibited the ability to inhibit C. albicans hyphae formation. In addition, (R)-3-hydroxyoctanoic and (E)-oct-2-enoic acids inhibited quorum sensing-regulated pyocyanin production in the opportunistic pathogen Pseudomonas aeruginosa PAO1. Generally, derivatives did not inhibit mammalian cell proliferation even at 3-mM concentrations, while only (E)-oct-2-enoic and 3-oxooctanoic acid had IC50 values of 1.7 and 1.6 mM with the human lung fibroblast cell line.

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Acknowledgments

This work has been financially supported by the Ministry of Education and Science, Republic of Serbia, under Grant No. 173048. JR was partially supported by research project BP2013 (Bioplastech Ltd., Dublin, Ireland).

Conflict of interest

The authors declare that they have no competing interests.

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  1. Maciej Guzik

    Present address: Jerzy Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, Niezapominajek 8, 30-239, Cracow, Poland

Authors and Affiliations

  1. Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, P.O. Box 23, Belgrade, 11010, Serbia

    Jelena Radivojevic, Lidija Senerovic & Branka Vasiljevic

  2. Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, Belgrade, Serbia

    Jelena Radivojevic, Sanja Skaro, Veselin Maslak & Jasmina Nikodinovic-Runic

  3. Bioplastech, NovaUCD, Belfield Innovation Park, Belfield, Dublin 4, Ireland

    Maciej Guzik, Shane T. Kenny & Kevin E. O’Connor

  4. University College Dublin, Belfield, Dublin 4, Ireland

    Kevin E. O’Connor

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  1. Jelena Radivojevic
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  2. Sanja Skaro
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Correspondence to Jasmina Nikodinovic-Runic or Kevin E. O’Connor.

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Electronic Supplementary Information (ESI) available: [Spectral Data 1H NMR, 13C NMR and IR]. (PDF 1614 kb)

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Radivojevic, J., Skaro, S., Senerovic, L. et al. Polyhydroxyalkanoate-based 3-hydroxyoctanoic acid and its derivatives as a platform of bioactive compounds. Appl Microbiol Biotechnol 100, 161–172 (2016). https://doi.org/10.1007/s00253-015-6984-4

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