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Structure-Activity Relationships of 3,3′-Phenylmethylene-bis-4-hydroxycoumarins: Selective and Potent Inhibitors of Gram-Positive Bacteria

Dicoumarols and coumarin derivatives have shown a variety of pharmaceutical activities and have been found to be potent inhibitor for the NAD(P)H-dependent flavoproteins. In this report, dicoumarol and its derivatives containing the substituted benzene ring at the methylenebis position were synthesi...

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Autores principales: Petnapapun, Kanokporn, Chavasiri, Warinthorn, Sompornpisut, Pornthep
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3891237/
https://www.ncbi.nlm.nih.gov/pubmed/24459419
http://dx.doi.org/10.1155/2013/178649
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author Petnapapun, Kanokporn
Chavasiri, Warinthorn
Sompornpisut, Pornthep
author_facet Petnapapun, Kanokporn
Chavasiri, Warinthorn
Sompornpisut, Pornthep
author_sort Petnapapun, Kanokporn
collection PubMed
description Dicoumarols and coumarin derivatives have shown a variety of pharmaceutical activities and have been found to be potent inhibitor for the NAD(P)H-dependent flavoproteins. In this report, dicoumarol and its derivatives containing the substituted benzene ring at the methylenebis position were synthesized and evaluated for their antibacterial activity against gram-positive bacteria: Staphylococcus aureus and Bacillus subtilis, and gram-negative bacteria: Escherichia coli and Klebsiella sp. The results showed that the synthesized dicoumarols affect cell growth but are selective against gram-positive over gram-negative bacterial cells. However, for most derivatives, the substitution of steric bulky benzene group on the methylenebis position appears to decrease in the efficacy of antibacterial effect. This finding is roughly described by the predicted poorer docked structure of the derivatives to a homology model of S. aureus flavoprotein. 3D-QSAR study highlighted structural features around the substituted benzene ring of dicoumarols as the antibacterial activity. CoMFA and CoMSIA contour maps support the idea that steric repulsion at the para position could diminish the antibacterial activity. The results of this study provide a better understanding of the molecular basis for the antibacterial activity of dicoumarols.
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spelling pubmed-38912372014-01-23 Structure-Activity Relationships of 3,3′-Phenylmethylene-bis-4-hydroxycoumarins: Selective and Potent Inhibitors of Gram-Positive Bacteria Petnapapun, Kanokporn Chavasiri, Warinthorn Sompornpisut, Pornthep ScientificWorldJournal Research Article Dicoumarols and coumarin derivatives have shown a variety of pharmaceutical activities and have been found to be potent inhibitor for the NAD(P)H-dependent flavoproteins. In this report, dicoumarol and its derivatives containing the substituted benzene ring at the methylenebis position were synthesized and evaluated for their antibacterial activity against gram-positive bacteria: Staphylococcus aureus and Bacillus subtilis, and gram-negative bacteria: Escherichia coli and Klebsiella sp. The results showed that the synthesized dicoumarols affect cell growth but are selective against gram-positive over gram-negative bacterial cells. However, for most derivatives, the substitution of steric bulky benzene group on the methylenebis position appears to decrease in the efficacy of antibacterial effect. This finding is roughly described by the predicted poorer docked structure of the derivatives to a homology model of S. aureus flavoprotein. 3D-QSAR study highlighted structural features around the substituted benzene ring of dicoumarols as the antibacterial activity. CoMFA and CoMSIA contour maps support the idea that steric repulsion at the para position could diminish the antibacterial activity. The results of this study provide a better understanding of the molecular basis for the antibacterial activity of dicoumarols. Hindawi Publishing Corporation 2013-12-29 /pmc/articles/PMC3891237/ /pubmed/24459419 http://dx.doi.org/10.1155/2013/178649 Text en Copyright © 2013 Kanokporn Petnapapun et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Petnapapun, Kanokporn
Chavasiri, Warinthorn
Sompornpisut, Pornthep
Structure-Activity Relationships of 3,3′-Phenylmethylene-bis-4-hydroxycoumarins: Selective and Potent Inhibitors of Gram-Positive Bacteria
title Structure-Activity Relationships of 3,3′-Phenylmethylene-bis-4-hydroxycoumarins: Selective and Potent Inhibitors of Gram-Positive Bacteria
title_full Structure-Activity Relationships of 3,3′-Phenylmethylene-bis-4-hydroxycoumarins: Selective and Potent Inhibitors of Gram-Positive Bacteria
title_fullStr Structure-Activity Relationships of 3,3′-Phenylmethylene-bis-4-hydroxycoumarins: Selective and Potent Inhibitors of Gram-Positive Bacteria
title_full_unstemmed Structure-Activity Relationships of 3,3′-Phenylmethylene-bis-4-hydroxycoumarins: Selective and Potent Inhibitors of Gram-Positive Bacteria
title_short Structure-Activity Relationships of 3,3′-Phenylmethylene-bis-4-hydroxycoumarins: Selective and Potent Inhibitors of Gram-Positive Bacteria
title_sort structure-activity relationships of 3,3′-phenylmethylene-bis-4-hydroxycoumarins: selective and potent inhibitors of gram-positive bacteria
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3891237/
https://www.ncbi.nlm.nih.gov/pubmed/24459419
http://dx.doi.org/10.1155/2013/178649
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