Solid-phase synthesis and biological evaluation of piperazine-based novel bacterial topoisomerase inhibitors

Research output: Contribution to journal › Journal article › Research › peer-review

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Solid-phase synthesis and biological evaluation of piperazine-based novel bacterial topoisomerase inhibitors. / Flagstad, Thomas; Pedersen, Mette T.; Jakobsen, Tim H.; Felding, Jakob; Tolker-Nielsen, Tim; Givskov, Michael; Qvortrup, Katrine; Nielsen, Thomas E.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 57, 128499, 2022.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Flagstad, T, Pedersen, MT, Jakobsen, TH, Felding, J, Tolker-Nielsen, T, Givskov, M, Qvortrup, K & Nielsen, TE 2022, 'Solid-phase synthesis and biological evaluation of piperazine-based novel bacterial topoisomerase inhibitors', Bioorganic and Medicinal Chemistry Letters, vol. 57, 128499. https://doi.org/10.1016/j.bmcl.2021.128499

APA

Flagstad, T., Pedersen, M. T., Jakobsen, T. H., Felding, J., Tolker-Nielsen, T., Givskov, M., Qvortrup, K., & Nielsen, T. E. (2022). Solid-phase synthesis and biological evaluation of piperazine-based novel bacterial topoisomerase inhibitors. Bioorganic and Medicinal Chemistry Letters, 57, [128499]. https://doi.org/10.1016/j.bmcl.2021.128499

Vancouver

Flagstad T, Pedersen MT, Jakobsen TH, Felding J, Tolker-Nielsen T, Givskov M et al. Solid-phase synthesis and biological evaluation of piperazine-based novel bacterial topoisomerase inhibitors. Bioorganic and Medicinal Chemistry Letters. 2022;57. 128499. https://doi.org/10.1016/j.bmcl.2021.128499

Author

Flagstad, Thomas ; Pedersen, Mette T. ; Jakobsen, Tim H. ; Felding, Jakob ; Tolker-Nielsen, Tim ; Givskov, Michael ; Qvortrup, Katrine ; Nielsen, Thomas E. / Solid-phase synthesis and biological evaluation of piperazine-based novel bacterial topoisomerase inhibitors. In: Bioorganic and Medicinal Chemistry Letters. 2022 ; Vol. 57.

Bibtex

@article{b50ac13f4a934be78d323115e02305ca,
title = "Solid-phase synthesis and biological evaluation of piperazine-based novel bacterial topoisomerase inhibitors",
abstract = "There is an emerging global need for new and more effective antibiotics against multi-resistant bacteria. This situation has led to massive industrial investigations on novel bacterial topoisomerase inhibitors (NBTIs) that target the vital bacterial enzymes DNA gyrase and topoisomerase IV. However, several of the NBTI compound classes have been associated with inhibition of the hERG potassium channel, an undesired cause of cardiac arrhythmia, which challenges medicinal chemistry efforts through lengthy synthetic routes. We herein present a solid-phase strategy that rapidly facilitates the chemical synthesis of a promising new class of NBTIs. A proof-of-concept library was synthesized with the ability to modulate both hERG affinity and antibacterial activity through scaffold substitutions.",
keywords = "Antibiotics, Bacterial Topoisomerase Inhibitors (NBTIs), hERG potassium channel, SAR study, Solid-phase synthesis",
author = "Thomas Flagstad and Pedersen, {Mette T.} and Jakobsen, {Tim H.} and Jakob Felding and Tim Tolker-Nielsen and Michael Givskov and Katrine Qvortrup and Nielsen, {Thomas E.}",
note = "Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2022",
doi = "10.1016/j.bmcl.2021.128499",
language = "English",
volume = "57",
journal = "Bioorganic & Medicinal Chemistry Letters",
issn = "0960-894X",
publisher = "Pergamon Press",

}

RIS

TY - JOUR

T1 - Solid-phase synthesis and biological evaluation of piperazine-based novel bacterial topoisomerase inhibitors

AU - Flagstad, Thomas

AU - Pedersen, Mette T.

AU - Jakobsen, Tim H.

AU - Felding, Jakob

AU - Tolker-Nielsen, Tim

AU - Givskov, Michael

AU - Qvortrup, Katrine

AU - Nielsen, Thomas E.

N1 - Publisher Copyright: © 2021 The Authors

PY - 2022

Y1 - 2022

N2 - There is an emerging global need for new and more effective antibiotics against multi-resistant bacteria. This situation has led to massive industrial investigations on novel bacterial topoisomerase inhibitors (NBTIs) that target the vital bacterial enzymes DNA gyrase and topoisomerase IV. However, several of the NBTI compound classes have been associated with inhibition of the hERG potassium channel, an undesired cause of cardiac arrhythmia, which challenges medicinal chemistry efforts through lengthy synthetic routes. We herein present a solid-phase strategy that rapidly facilitates the chemical synthesis of a promising new class of NBTIs. A proof-of-concept library was synthesized with the ability to modulate both hERG affinity and antibacterial activity through scaffold substitutions.

AB - There is an emerging global need for new and more effective antibiotics against multi-resistant bacteria. This situation has led to massive industrial investigations on novel bacterial topoisomerase inhibitors (NBTIs) that target the vital bacterial enzymes DNA gyrase and topoisomerase IV. However, several of the NBTI compound classes have been associated with inhibition of the hERG potassium channel, an undesired cause of cardiac arrhythmia, which challenges medicinal chemistry efforts through lengthy synthetic routes. We herein present a solid-phase strategy that rapidly facilitates the chemical synthesis of a promising new class of NBTIs. A proof-of-concept library was synthesized with the ability to modulate both hERG affinity and antibacterial activity through scaffold substitutions.

KW - Antibiotics

KW - Bacterial Topoisomerase Inhibitors (NBTIs)

KW - hERG potassium channel

KW - SAR study

KW - Solid-phase synthesis

U2 - 10.1016/j.bmcl.2021.128499

DO - 10.1016/j.bmcl.2021.128499

M3 - Journal article

C2 - 34906671

AN - SCOPUS:85121513097

VL - 57

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

SN - 0960-894X

M1 - 128499

ER -

ID: 288714419