title: Polyhydroxyalkanoate-based 3-hydroxyoctanoic acid and its derivatives as a platform of bioactive compounds.
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.
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, P.O. Box 23, Belgrade, 11010, Serbia.|Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, Belgrade, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Radivojevic
authors.affiliation: Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, Belgrade, Serbia.
authors.forename: Sanja
authors.initials: S
authors.lastname: Skaro
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, P.O. Box 23, Belgrade, 11010, Serbia.
authors.forename: Lidija
authors.initials: L
authors.lastname: Senerovic
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, P.O. Box 23, Belgrade, 11010, Serbia.
authors.forename: Branka
authors.initials: B
authors.lastname: Vasiljevic
authors.affiliation: Bioplastech, NovaUCD, Belfield Innovation Park, Belfield, Dublin 4, Ireland.|Jerzy Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, Niezapominajek 8, 30-239, Cracow, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Guzik
authors.affiliation: Bioplastech, NovaUCD, Belfield Innovation Park, Belfield, Dublin 4, Ireland.
authors.forename: Shane T
authors.initials: ST
authors.lastname: Kenny
authors.affiliation: Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, Belgrade, Serbia.
authors.forename: Veselin
authors.initials: V
authors.lastname: Maslak
authors.affiliation: Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, Belgrade, Serbia. jasmina.nikodinovic@imgge.bg.ac.rs.
authors.forename: Jasmina
authors.initials: J
authors.lastname: Nikodinovic-Runic
authors.affiliation: Bioplastech, NovaUCD, Belfield Innovation Park, Belfield, Dublin 4, Ireland. Kevin.oconnor@ucd.ie.|University College Dublin, Belfield, Dublin 4, Ireland. Kevin.oconnor@ucd.ie.
authors.forename: Kevin E
authors.initials: KE
authors.lastname: O'Connor
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000378:metabolism*; D001419:Bacteria / Q000187:drug effects; D001711:Biotransformation; D002210:Caprylates / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D005658:Fungi / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008322:Mammals; D008826:Microbial Sensitivity Tests; D054813:Polyhydroxyalkanoates / Q000378:metabolism*; D011710:Pyocyanine / Q000037:antagonists & inhibitors
chemical_list: D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D002210:Caprylates; D054813:Polyhydroxyalkanoates; C101940:3-hydroxyoctanoic acid; D011710:Pyocyanine
keywords: (R)-3-Hydroxyalkanoic acids; Antimicrobial activity; Chemical derivatization; Polyhydroxyalkanoate