Multisubstituted pyrimidines effectively inhibit bacterial growth and biofilm formation of Staphylococcus aureus
Abstract Biofilms are multicellular communities of microorganisms that generally attach to surfaces in a self-produced matrix. Unlike planktonic cells, biofilms can withstand conventional antibiotics, causing significant challenges in the healthcare system. Currently, new chemical entities are urgen...
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2021
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oai:doaj.org-article:31c6533710d348fb836b7b06e81689d32021-12-02T15:51:13ZMultisubstituted pyrimidines effectively inhibit bacterial growth and biofilm formation of Staphylococcus aureus10.1038/s41598-021-86852-52045-2322https://doaj.org/article/31c6533710d348fb836b7b06e81689d32021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86852-5https://doaj.org/toc/2045-2322Abstract Biofilms are multicellular communities of microorganisms that generally attach to surfaces in a self-produced matrix. Unlike planktonic cells, biofilms can withstand conventional antibiotics, causing significant challenges in the healthcare system. Currently, new chemical entities are urgently needed to develop novel anti-biofilm agents. In this study, we designed and synthesized a set of 2,4,5,6-tetrasubstituted pyrimidines and assessed their antibacterial activity against planktonic cells and biofilms formed by Staphylococcus aureus. Compounds 9e, 10d, and 10e displayed potent activity for inhibiting the onset of biofilm formation as well as for killing pre-formed biofilms of S. aureus ATCC 25923 and Newman strains, with half-maximal inhibitory concentration (IC50) values ranging from 11.6 to 62.0 µM. These pyrimidines, at 100 µM, not only decreased the number of viable bacteria within the pre-formed biofilm by 2–3 log10 but also reduced the amount of total biomass by 30–50%. Furthermore, these compounds were effective against planktonic cells with minimum inhibitory concentration (MIC) values lower than 60 µM for both staphylococcal strains. Compound 10d inhibited the growth of S. aureus ATCC 25923 in a concentration-dependent manner and displayed a bactericidal anti-staphylococcal activity. Taken together, our study highlights the value of multisubstituted pyrimidines to develop novel anti-biofilm agents.Riccardo ProvenzaniPaola San-Martin-GalindoGhada HassanAshenafi LegeharAleksi KallioHenri XhaardAdyary FallareroJari Yli-KauhaluomaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021) |
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Medicine R Science Q Riccardo Provenzani Paola San-Martin-Galindo Ghada Hassan Ashenafi Legehar Aleksi Kallio Henri Xhaard Adyary Fallarero Jari Yli-Kauhaluoma Multisubstituted pyrimidines effectively inhibit bacterial growth and biofilm formation of Staphylococcus aureus |
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Abstract Biofilms are multicellular communities of microorganisms that generally attach to surfaces in a self-produced matrix. Unlike planktonic cells, biofilms can withstand conventional antibiotics, causing significant challenges in the healthcare system. Currently, new chemical entities are urgently needed to develop novel anti-biofilm agents. In this study, we designed and synthesized a set of 2,4,5,6-tetrasubstituted pyrimidines and assessed their antibacterial activity against planktonic cells and biofilms formed by Staphylococcus aureus. Compounds 9e, 10d, and 10e displayed potent activity for inhibiting the onset of biofilm formation as well as for killing pre-formed biofilms of S. aureus ATCC 25923 and Newman strains, with half-maximal inhibitory concentration (IC50) values ranging from 11.6 to 62.0 µM. These pyrimidines, at 100 µM, not only decreased the number of viable bacteria within the pre-formed biofilm by 2–3 log10 but also reduced the amount of total biomass by 30–50%. Furthermore, these compounds were effective against planktonic cells with minimum inhibitory concentration (MIC) values lower than 60 µM for both staphylococcal strains. Compound 10d inhibited the growth of S. aureus ATCC 25923 in a concentration-dependent manner and displayed a bactericidal anti-staphylococcal activity. Taken together, our study highlights the value of multisubstituted pyrimidines to develop novel anti-biofilm agents. |
format |
article |
author |
Riccardo Provenzani Paola San-Martin-Galindo Ghada Hassan Ashenafi Legehar Aleksi Kallio Henri Xhaard Adyary Fallarero Jari Yli-Kauhaluoma |
author_facet |
Riccardo Provenzani Paola San-Martin-Galindo Ghada Hassan Ashenafi Legehar Aleksi Kallio Henri Xhaard Adyary Fallarero Jari Yli-Kauhaluoma |
author_sort |
Riccardo Provenzani |
title |
Multisubstituted pyrimidines effectively inhibit bacterial growth and biofilm formation of Staphylococcus aureus |
title_short |
Multisubstituted pyrimidines effectively inhibit bacterial growth and biofilm formation of Staphylococcus aureus |
title_full |
Multisubstituted pyrimidines effectively inhibit bacterial growth and biofilm formation of Staphylococcus aureus |
title_fullStr |
Multisubstituted pyrimidines effectively inhibit bacterial growth and biofilm formation of Staphylococcus aureus |
title_full_unstemmed |
Multisubstituted pyrimidines effectively inhibit bacterial growth and biofilm formation of Staphylococcus aureus |
title_sort |
multisubstituted pyrimidines effectively inhibit bacterial growth and biofilm formation of staphylococcus aureus |
publisher |
Nature Portfolio |
publishDate |
2021 |
url |
https://doaj.org/article/31c6533710d348fb836b7b06e81689d3 |
work_keys_str_mv |
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