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Integrated in vitro-in silico screening strategy for the discovery of antibacterial compounds

Tutkimustuotosvertaisarvioitu

Standard

Integrated in vitro-in silico screening strategy for the discovery of antibacterial compounds. / Nybond, Susanna; Ghemtio, Leo; Nawrot, Dorota A.; Karp, Matti; Xhaard, Henri; Tammela, Päivi.

julkaisussa: Assay and Drug Development Technologies, Vuosikerta 13, Nro 1, 01.02.2015, s. 25-33.

Tutkimustuotosvertaisarvioitu

Harvard

Nybond, S, Ghemtio, L, Nawrot, DA, Karp, M, Xhaard, H & Tammela, P 2015, 'Integrated in vitro-in silico screening strategy for the discovery of antibacterial compounds', Assay and Drug Development Technologies, Vuosikerta. 13, Nro 1, Sivut 25-33. https://doi.org/10.1089/adt.2014.625

APA

Nybond, S., Ghemtio, L., Nawrot, D. A., Karp, M., Xhaard, H., & Tammela, P. (2015). Integrated in vitro-in silico screening strategy for the discovery of antibacterial compounds. Assay and Drug Development Technologies, 13(1), 25-33. https://doi.org/10.1089/adt.2014.625

Vancouver

Nybond S, Ghemtio L, Nawrot DA, Karp M, Xhaard H, Tammela P. Integrated in vitro-in silico screening strategy for the discovery of antibacterial compounds. Assay and Drug Development Technologies. 2015 helmi 1;13(1):25-33. https://doi.org/10.1089/adt.2014.625

Author

Nybond, Susanna ; Ghemtio, Leo ; Nawrot, Dorota A. ; Karp, Matti ; Xhaard, Henri ; Tammela, Päivi. / Integrated in vitro-in silico screening strategy for the discovery of antibacterial compounds. Julkaisussa: Assay and Drug Development Technologies. 2015 ; Vuosikerta 13, Nro 1. Sivut 25-33.

Bibtex - Lataa

@article{8a5be94b318346dbb430ec41056bfaae,
title = "Integrated in vitro-in silico screening strategy for the discovery of antibacterial compounds",
abstract = "Multidrug-resistant bacterial infections are an increasing source of healthcare problems, and the research for new antibiotics is currently unable to respond to this challenge. In this work, we present a screening strategy that integrates cell-based high-throughput screening (HTS) with in silico analogue search for antimicrobial small-molecule drug discovery. We performed an HTS on a diverse chemical library by using an assay based on a bioluminescent Escherichia coli K-12 (pTetLux1) strain. The HTS yielded eight hit compounds with >50{\%} inhibition. These hits were then used for structural similarity-based virtual screening, and of the 29 analogues selected for in vitro testing, four compounds displayed potential activity in the pTetLux1 assay. The 11 most active compounds from combined HTS and analogue search were further assessed for antimicrobial activity against clinically important strains of E. coli and Staphylococcus aureus and for in vitro cytotoxicity against human cells. Three of the compounds displayed antibacterial activity and low human cell cytotoxicity. Additionally, two compounds of the set fully inhibited S. aureus growth after 24 h, but also exhibited human cell cytotoxicity in vitro.",
author = "Susanna Nybond and Leo Ghemtio and Nawrot, {Dorota A.} and Matti Karp and Henri Xhaard and P{\"a}ivi Tammela",
year = "2015",
month = "2",
day = "1",
doi = "10.1089/adt.2014.625",
language = "English",
volume = "13",
pages = "25--33",
journal = "Assay and Drug Development Technologies",
issn = "1540-658X",
publisher = "Mary Ann Liebert",
number = "1",

}

RIS (suitable for import to EndNote) - Lataa

TY - JOUR

T1 - Integrated in vitro-in silico screening strategy for the discovery of antibacterial compounds

AU - Nybond, Susanna

AU - Ghemtio, Leo

AU - Nawrot, Dorota A.

AU - Karp, Matti

AU - Xhaard, Henri

AU - Tammela, Päivi

PY - 2015/2/1

Y1 - 2015/2/1

N2 - Multidrug-resistant bacterial infections are an increasing source of healthcare problems, and the research for new antibiotics is currently unable to respond to this challenge. In this work, we present a screening strategy that integrates cell-based high-throughput screening (HTS) with in silico analogue search for antimicrobial small-molecule drug discovery. We performed an HTS on a diverse chemical library by using an assay based on a bioluminescent Escherichia coli K-12 (pTetLux1) strain. The HTS yielded eight hit compounds with >50% inhibition. These hits were then used for structural similarity-based virtual screening, and of the 29 analogues selected for in vitro testing, four compounds displayed potential activity in the pTetLux1 assay. The 11 most active compounds from combined HTS and analogue search were further assessed for antimicrobial activity against clinically important strains of E. coli and Staphylococcus aureus and for in vitro cytotoxicity against human cells. Three of the compounds displayed antibacterial activity and low human cell cytotoxicity. Additionally, two compounds of the set fully inhibited S. aureus growth after 24 h, but also exhibited human cell cytotoxicity in vitro.

AB - Multidrug-resistant bacterial infections are an increasing source of healthcare problems, and the research for new antibiotics is currently unable to respond to this challenge. In this work, we present a screening strategy that integrates cell-based high-throughput screening (HTS) with in silico analogue search for antimicrobial small-molecule drug discovery. We performed an HTS on a diverse chemical library by using an assay based on a bioluminescent Escherichia coli K-12 (pTetLux1) strain. The HTS yielded eight hit compounds with >50% inhibition. These hits were then used for structural similarity-based virtual screening, and of the 29 analogues selected for in vitro testing, four compounds displayed potential activity in the pTetLux1 assay. The 11 most active compounds from combined HTS and analogue search were further assessed for antimicrobial activity against clinically important strains of E. coli and Staphylococcus aureus and for in vitro cytotoxicity against human cells. Three of the compounds displayed antibacterial activity and low human cell cytotoxicity. Additionally, two compounds of the set fully inhibited S. aureus growth after 24 h, but also exhibited human cell cytotoxicity in vitro.

UR - http://www.scopus.com/inward/record.url?scp=84923872765&partnerID=8YFLogxK

U2 - 10.1089/adt.2014.625

DO - 10.1089/adt.2014.625

M3 - Article

VL - 13

SP - 25

EP - 33

JO - Assay and Drug Development Technologies

JF - Assay and Drug Development Technologies

SN - 1540-658X

IS - 1

ER -