Enantioselectivity of Chiral Derivatives of Xanthones in Virulence Effects of Resistant Bacteria

Antimicrobial peptides are one of the lines of defense produced by several hosts in response to bacterial infections. Inspired by them and recent discoveries of xanthones as bacterial efflux pump inhibitors, chiral amides with a xanthone scaffold were planned to be potential antimicrobial adjuvants....

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Autores principales:	Fernando Durães, Sara Cravo, Joana Freitas-Silva, Nikoletta Szemerédi, Paulo Martins-da-Costa, Eugénia Pinto, Maria Elizabeth Tiritan, Gabriella Spengler, Carla Fernandes, Emília Sousa, Madalena Pinto
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	xanthones chiral antibacterial efflux pumps biofilm quorum-sensing Medicine R Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/a7abe5ef10784e8cbb60ef22a03b49a7
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spelling	oai:doaj.org-article:a7abe5ef10784e8cbb60ef22a03b49a72021-11-25T18:39:40ZEnantioselectivity of Chiral Derivatives of Xanthones in Virulence Effects of Resistant Bacteria10.3390/ph141111411424-8247https://doaj.org/article/a7abe5ef10784e8cbb60ef22a03b49a72021-11-01T00:00:00Zhttps://www.mdpi.com/1424-8247/14/11/1141https://doaj.org/toc/1424-8247Antimicrobial peptides are one of the lines of defense produced by several hosts in response to bacterial infections. Inspired by them and recent discoveries of xanthones as bacterial efflux pump inhibitors, chiral amides with a xanthone scaffold were planned to be potential antimicrobial adjuvants. The chiral derivatives of xanthones were obtained by peptide coupling reactions between suitable xanthones with enantiomerically pure building blocks, yielding derivatives with high enantiomeric purity. Among 18 compounds investigated for their antimicrobial activity against reference strains of bacteria and fungi, antibacterial activity for the tested strains was not found. Selected compounds were also evaluated for their potential to inhibit bacterial efflux pumps. Compound <b>(<i>R</i>,<i>R</i>)-8</b> inhibited efflux pumps in the Gram-positive model tested and three compounds, <b>(<i>S</i>,<i>S</i>)-8</b>, <b>(<i>R</i>)-17</b> and <b>(<i>R</i>,<i>S</i>)-18</b>, displayed the same activity in the Gram-negative strain used. Studies were performed on the inhibition of biofilm formation and quorum-sensing, to which the enantiomeric pair <b>8</b> displayed activity for the latter. To gain a better understanding of how the active compounds bind to the efflux pumps, docking studies were performed. Hit compounds were proposed for each activity, and it was shown that enantioselectivity was noticeable and must be considered, as enantiomers displayed differences in activity.Fernando DurãesSara CravoJoana Freitas-SilvaNikoletta SzemerédiPaulo Martins-da-CostaEugénia PintoMaria Elizabeth TiritanGabriella SpenglerCarla FernandesEmília SousaMadalena PintoMDPI AGarticlexanthoneschiralantibacterialefflux pumpsbiofilmquorum-sensingMedicineRPharmacy and materia medicaRS1-441ENPharmaceuticals, Vol 14, Iss 1141, p 1141 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	xanthones chiral antibacterial efflux pumps biofilm quorum-sensing Medicine R Pharmacy and materia medica RS1-441
spellingShingle	xanthones chiral antibacterial efflux pumps biofilm quorum-sensing Medicine R Pharmacy and materia medica RS1-441 Fernando Durães Sara Cravo Joana Freitas-Silva Nikoletta Szemerédi Paulo Martins-da-Costa Eugénia Pinto Maria Elizabeth Tiritan Gabriella Spengler Carla Fernandes Emília Sousa Madalena Pinto Enantioselectivity of Chiral Derivatives of Xanthones in Virulence Effects of Resistant Bacteria
description	Antimicrobial peptides are one of the lines of defense produced by several hosts in response to bacterial infections. Inspired by them and recent discoveries of xanthones as bacterial efflux pump inhibitors, chiral amides with a xanthone scaffold were planned to be potential antimicrobial adjuvants. The chiral derivatives of xanthones were obtained by peptide coupling reactions between suitable xanthones with enantiomerically pure building blocks, yielding derivatives with high enantiomeric purity. Among 18 compounds investigated for their antimicrobial activity against reference strains of bacteria and fungi, antibacterial activity for the tested strains was not found. Selected compounds were also evaluated for their potential to inhibit bacterial efflux pumps. Compound <b>(<i>R</i>,<i>R</i>)-8</b> inhibited efflux pumps in the Gram-positive model tested and three compounds, <b>(<i>S</i>,<i>S</i>)-8</b>, <b>(<i>R</i>)-17</b> and <b>(<i>R</i>,<i>S</i>)-18</b>, displayed the same activity in the Gram-negative strain used. Studies were performed on the inhibition of biofilm formation and quorum-sensing, to which the enantiomeric pair <b>8</b> displayed activity for the latter. To gain a better understanding of how the active compounds bind to the efflux pumps, docking studies were performed. Hit compounds were proposed for each activity, and it was shown that enantioselectivity was noticeable and must be considered, as enantiomers displayed differences in activity.
format	article
author	Fernando Durães Sara Cravo Joana Freitas-Silva Nikoletta Szemerédi Paulo Martins-da-Costa Eugénia Pinto Maria Elizabeth Tiritan Gabriella Spengler Carla Fernandes Emília Sousa Madalena Pinto
author_facet	Fernando Durães Sara Cravo Joana Freitas-Silva Nikoletta Szemerédi Paulo Martins-da-Costa Eugénia Pinto Maria Elizabeth Tiritan Gabriella Spengler Carla Fernandes Emília Sousa Madalena Pinto
author_sort	Fernando Durães
title	Enantioselectivity of Chiral Derivatives of Xanthones in Virulence Effects of Resistant Bacteria
title_short	Enantioselectivity of Chiral Derivatives of Xanthones in Virulence Effects of Resistant Bacteria
title_full	Enantioselectivity of Chiral Derivatives of Xanthones in Virulence Effects of Resistant Bacteria
title_fullStr	Enantioselectivity of Chiral Derivatives of Xanthones in Virulence Effects of Resistant Bacteria
title_full_unstemmed	Enantioselectivity of Chiral Derivatives of Xanthones in Virulence Effects of Resistant Bacteria
title_sort	enantioselectivity of chiral derivatives of xanthones in virulence effects of resistant bacteria
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/a7abe5ef10784e8cbb60ef22a03b49a7
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Enantioselectivity of Chiral Derivatives of Xanthones in Virulence Effects of Resistant Bacteria

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