Insights into the molecular properties underlying antibacterial activity of prenylated (iso)flavonoids against MRSA

Abstract High resistance towards traditional antibiotics has urged the development of new, natural therapeutics against methicillin-resistant Staphylococcus aureus (MRSA). Prenylated (iso)flavonoids, present mainly in the Fabaceae, can serve as promising candidates. Herein, the anti-MRSA properties...

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Autores principales:	Sylvia Kalli, Carla Araya-Cloutier, Jos Hageman, Jean-Paul Vincken
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0407b3d95ffb40129fa0ded605801a35
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spelling	oai:doaj.org-article:0407b3d95ffb40129fa0ded605801a352021-12-02T15:23:08ZInsights into the molecular properties underlying antibacterial activity of prenylated (iso)flavonoids against MRSA10.1038/s41598-021-92964-92045-2322https://doaj.org/article/0407b3d95ffb40129fa0ded605801a352021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92964-9https://doaj.org/toc/2045-2322Abstract High resistance towards traditional antibiotics has urged the development of new, natural therapeutics against methicillin-resistant Staphylococcus aureus (MRSA). Prenylated (iso)flavonoids, present mainly in the Fabaceae, can serve as promising candidates. Herein, the anti-MRSA properties of 23 prenylated (iso)flavonoids were assessed in-vitro. The di-prenylated (iso)flavonoids, glabrol (flavanone) and 6,8-diprenyl genistein (isoflavone), together with the mono-prenylated, 4′-O-methyl glabridin (isoflavan), were the most active anti-MRSA compounds (Minimum Inhibitory Concentrations (MIC) ≤ 10 µg/mL, 30 µM). The in-house activity data was complemented with literature data to yield an extended, curated dataset of 67 molecules for the development of robust in-silico prediction models. A QSAR model having a good fit (R2 adj 0.61), low average prediction errors and a good predictive power (Q2) for the training (4% and Q2 LOO 0.57, respectively) and the test set (5% and Q2 test 0.75, respectively) was obtained. Furthermore, the model predicted well the activity of an external validation set (on average 5% prediction errors), as well as the level of activity (low, moderate, high) of prenylated (iso)flavonoids against other Gram-positive bacteria. For the first time, the importance of formal charge, besides hydrophobic volume and hydrogen-bonding, in the anti-MRSA activity was highlighted, thereby suggesting potentially different modes of action of the different prenylated (iso)flavonoids.Sylvia KalliCarla Araya-CloutierJos HagemanJean-Paul VinckenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sylvia Kalli Carla Araya-Cloutier Jos Hageman Jean-Paul Vincken Insights into the molecular properties underlying antibacterial activity of prenylated (iso)flavonoids against MRSA
description	Abstract High resistance towards traditional antibiotics has urged the development of new, natural therapeutics against methicillin-resistant Staphylococcus aureus (MRSA). Prenylated (iso)flavonoids, present mainly in the Fabaceae, can serve as promising candidates. Herein, the anti-MRSA properties of 23 prenylated (iso)flavonoids were assessed in-vitro. The di-prenylated (iso)flavonoids, glabrol (flavanone) and 6,8-diprenyl genistein (isoflavone), together with the mono-prenylated, 4′-O-methyl glabridin (isoflavan), were the most active anti-MRSA compounds (Minimum Inhibitory Concentrations (MIC) ≤ 10 µg/mL, 30 µM). The in-house activity data was complemented with literature data to yield an extended, curated dataset of 67 molecules for the development of robust in-silico prediction models. A QSAR model having a good fit (R2 adj 0.61), low average prediction errors and a good predictive power (Q2) for the training (4% and Q2 LOO 0.57, respectively) and the test set (5% and Q2 test 0.75, respectively) was obtained. Furthermore, the model predicted well the activity of an external validation set (on average 5% prediction errors), as well as the level of activity (low, moderate, high) of prenylated (iso)flavonoids against other Gram-positive bacteria. For the first time, the importance of formal charge, besides hydrophobic volume and hydrogen-bonding, in the anti-MRSA activity was highlighted, thereby suggesting potentially different modes of action of the different prenylated (iso)flavonoids.
format	article
author	Sylvia Kalli Carla Araya-Cloutier Jos Hageman Jean-Paul Vincken
author_facet	Sylvia Kalli Carla Araya-Cloutier Jos Hageman Jean-Paul Vincken
author_sort	Sylvia Kalli
title	Insights into the molecular properties underlying antibacterial activity of prenylated (iso)flavonoids against MRSA
title_short	Insights into the molecular properties underlying antibacterial activity of prenylated (iso)flavonoids against MRSA
title_full	Insights into the molecular properties underlying antibacterial activity of prenylated (iso)flavonoids against MRSA
title_fullStr	Insights into the molecular properties underlying antibacterial activity of prenylated (iso)flavonoids against MRSA
title_full_unstemmed	Insights into the molecular properties underlying antibacterial activity of prenylated (iso)flavonoids against MRSA
title_sort	insights into the molecular properties underlying antibacterial activity of prenylated (iso)flavonoids against mrsa
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0407b3d95ffb40129fa0ded605801a35
work_keys_str_mv	AT sylviakalli insightsintothemolecularpropertiesunderlyingantibacterialactivityofprenylatedisoflavonoidsagainstmrsa AT carlaarayacloutier insightsintothemolecularpropertiesunderlyingantibacterialactivityofprenylatedisoflavonoidsagainstmrsa AT joshageman insightsintothemolecularpropertiesunderlyingantibacterialactivityofprenylatedisoflavonoidsagainstmrsa AT jeanpaulvincken insightsintothemolecularpropertiesunderlyingantibacterialactivityofprenylatedisoflavonoidsagainstmrsa
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Insights into the molecular properties underlying antibacterial activity of prenylated (iso)flavonoids against MRSA

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