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Molecular Biology Reports

, Volume 46, Issue 1, pp 51–58 | Cite as

Synthesis of terpenoid oxo derivatives with antiureolytic activity

  • Agata Kozioł
  • Katarzyna Macegoniuk
  • Ewa Grela
  • Agnieszka Grabowiecka
  • Monika Biernat
  • Stanisław LochyńskiEmail author
Original Article

Abstract

Urease is an important virulence factor for a variety of pathogenic bacteria strains such as Helicobacter pylori, which colonizes human gastric mucosa, and Proteus sp., responsible for urinary tract infections. Specific inhibition of urease activity could be a promising adjuvant strategy for eradication of these pathogens. Due to the interesting antiureolytic activity of carvone and the scant information regarding the inhibitory properties of corresponding monoterpenes, we decided to study selected monoterpenic ketones and their oxygen derivatives. Several monoterpenes and their terpenoid oxygen derivatives were evaluated in vitro against Sporosarcina pasteurii urease. The most effective inhibitors—derivatives of β-cyclocitral (ester 10 and bromolactone 14)—were described with \({K_i}\) of 46.7 µM and 45.8 µM, respectively. Active inhibitors of native urease were tested against H. pylori and Proteus mirabilis whole cells. Here, the most active inhibitor, 14, was characterized with IC50 values of 0.32 mM and 0.61 mM for P. mirabilis and H. pylori, respectively. The antibacterial activity of a few tested inhibitors was also observed. Compound 14 limited the growth of E. coli (\(MI{C_{50}}\)= 250 μg/mL). Interestingly, 10 was the only compound that was effective against both Gram-negative and Gram-positive bacteria. It had a \(MI{C_{50}}\) of 150 μg/mL against E. coli and S. aureus. In the presented study a group of novel antiureolytic compounds was characterised. Besides carvone stereoisomers, these are the only terpenoid urease inhibitors described so far.

Keywords

Terpenoid Antiureolytic activity Inhibitors Bacterial urease 

Notes

Funding

English editing was funded by the Wroclaw Centre of Biotechnology Program, The Leading National Research Centre (KNOW) for the years 2014–2018 (know.wroc.pl).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

11033_2018_4442_MOESM1_ESM.docx (1.8 mb)
Supplementary material 1 (DOCX 1799 KB)

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Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  • Agata Kozioł
    • 1
    • 2
  • Katarzyna Macegoniuk
    • 1
  • Ewa Grela
    • 1
  • Agnieszka Grabowiecka
    • 1
  • Monika Biernat
    • 3
  • Stanisław Lochyński
    • 1
    • 2
    Email author
  1. 1.Bioorganic Chemistry Department, Faculty of ChemistryWroclaw University of Science and TechnologyWrocławPoland
  2. 2.Institute of CosmetologyWrocław College of PhysiotherapyWrocławPoland
  3. 3.Department and Clinic of Haematology, Blood Neoplasms, and Bone Marrow TransplantationWrocław Medical UniversityWrocławPoland

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