Analogues of Disulfides from Allium stipitatum Demonstrate Potent Anti-tubercular Activities through Drug Efflux Pump and Biofilm Inhibition

Abstract Disulfides from Allium stipitatum, commonly known as Persian shallot, were previously reported to possess antibacterial properties. Analogues of these compounds, produced by S-methylthiolation of appropriate thiols using S-methyl methanethiosulfonate, exhibited antimicrobial activity, with...

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Autores principales: Cynthia A. Danquah, Eleftheria Kakagianni, Proma Khondkar, Arundhati Maitra, Mukhlesur Rahman, Dimitrios Evangelopoulos, Timothy D. McHugh, Paul Stapleton, John Malkinson, Sanjib Bhakta, Simon Gibbons
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Publicado: Nature Portfolio 2018
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spelling oai:doaj.org-article:37e1ab0ec36449f69d577c41c3e6f5462021-12-02T15:07:50ZAnalogues of Disulfides from Allium stipitatum Demonstrate Potent Anti-tubercular Activities through Drug Efflux Pump and Biofilm Inhibition10.1038/s41598-017-18948-w2045-2322https://doaj.org/article/37e1ab0ec36449f69d577c41c3e6f5462018-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-18948-whttps://doaj.org/toc/2045-2322Abstract Disulfides from Allium stipitatum, commonly known as Persian shallot, were previously reported to possess antibacterial properties. Analogues of these compounds, produced by S-methylthiolation of appropriate thiols using S-methyl methanethiosulfonate, exhibited antimicrobial activity, with one compound inhibiting the growth of Mycobacterium tuberculosis at 17 µM (4 mg L−1) and other compounds inhibiting Escherichia coli and multi-drug-resistant (MDR) Staphylococcus aureus at concentrations ranging between 32–138 µM (8–32 mg L−1). These compounds also displayed moderate inhibitory effects on Klebsiella and Proteus species. Whole-cell phenotypic bioassays such as the spot-culture growth inhibition assay (SPOTi), drug efflux inhibition, biofilm inhibition and cytotoxicity assays were used to evaluate these compounds. Of particular note was their ability to inhibit mycobacterial drug efflux and biofilm formation, while maintaining a high selectivity towards M. tuberculosis H37Rv. These results suggest that methyl disulfides are novel scaffolds which could lead to the development of new drugs against tuberculosis (TB).Cynthia A. DanquahEleftheria KakagianniProma KhondkarArundhati MaitraMukhlesur RahmanDimitrios EvangelopoulosTimothy D. McHughPaul StapletonJohn MalkinsonSanjib BhaktaSimon GibbonsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-7 (2018)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Cynthia A. Danquah
Eleftheria Kakagianni
Proma Khondkar
Arundhati Maitra
Mukhlesur Rahman
Dimitrios Evangelopoulos
Timothy D. McHugh
Paul Stapleton
John Malkinson
Sanjib Bhakta
Simon Gibbons
Analogues of Disulfides from Allium stipitatum Demonstrate Potent Anti-tubercular Activities through Drug Efflux Pump and Biofilm Inhibition
description Abstract Disulfides from Allium stipitatum, commonly known as Persian shallot, were previously reported to possess antibacterial properties. Analogues of these compounds, produced by S-methylthiolation of appropriate thiols using S-methyl methanethiosulfonate, exhibited antimicrobial activity, with one compound inhibiting the growth of Mycobacterium tuberculosis at 17 µM (4 mg L−1) and other compounds inhibiting Escherichia coli and multi-drug-resistant (MDR) Staphylococcus aureus at concentrations ranging between 32–138 µM (8–32 mg L−1). These compounds also displayed moderate inhibitory effects on Klebsiella and Proteus species. Whole-cell phenotypic bioassays such as the spot-culture growth inhibition assay (SPOTi), drug efflux inhibition, biofilm inhibition and cytotoxicity assays were used to evaluate these compounds. Of particular note was their ability to inhibit mycobacterial drug efflux and biofilm formation, while maintaining a high selectivity towards M. tuberculosis H37Rv. These results suggest that methyl disulfides are novel scaffolds which could lead to the development of new drugs against tuberculosis (TB).
format article
author Cynthia A. Danquah
Eleftheria Kakagianni
Proma Khondkar
Arundhati Maitra
Mukhlesur Rahman
Dimitrios Evangelopoulos
Timothy D. McHugh
Paul Stapleton
John Malkinson
Sanjib Bhakta
Simon Gibbons
author_facet Cynthia A. Danquah
Eleftheria Kakagianni
Proma Khondkar
Arundhati Maitra
Mukhlesur Rahman
Dimitrios Evangelopoulos
Timothy D. McHugh
Paul Stapleton
John Malkinson
Sanjib Bhakta
Simon Gibbons
author_sort Cynthia A. Danquah
title Analogues of Disulfides from Allium stipitatum Demonstrate Potent Anti-tubercular Activities through Drug Efflux Pump and Biofilm Inhibition
title_short Analogues of Disulfides from Allium stipitatum Demonstrate Potent Anti-tubercular Activities through Drug Efflux Pump and Biofilm Inhibition
title_full Analogues of Disulfides from Allium stipitatum Demonstrate Potent Anti-tubercular Activities through Drug Efflux Pump and Biofilm Inhibition
title_fullStr Analogues of Disulfides from Allium stipitatum Demonstrate Potent Anti-tubercular Activities through Drug Efflux Pump and Biofilm Inhibition
title_full_unstemmed Analogues of Disulfides from Allium stipitatum Demonstrate Potent Anti-tubercular Activities through Drug Efflux Pump and Biofilm Inhibition
title_sort analogues of disulfides from allium stipitatum demonstrate potent anti-tubercular activities through drug efflux pump and biofilm inhibition
publisher Nature Portfolio
publishDate 2018
url https://doaj.org/article/37e1ab0ec36449f69d577c41c3e6f546
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