Norbornane-based cationic antimicrobial peptidomimetics targeting the bacterial membrane

Shane M. Hickey; Trent D. Ashton; Gareth Boer; Christie A. Bader; Michael Thomas; Alysha G. Elliott; Carsten Schmuck; Heidi Y. Yu; Jian Li; Roger L. Nation; Matthew A. Cooper; Sally E. Plush; Douglas A. Brooks; Frederick M. Pfeffer

doi:10.1016/j.ejmech.2018.09.072

Norbornane-based cationic antimicrobial peptidomimetics targeting the bacterial membrane

Shane M. Hickey^*, Trent D. Ashton, Gareth Boer, Christie A. Bader, Michael Thomas, Alysha G. Elliott, Carsten Schmuck, Heidi Y. Yu, Jian Li, Roger L. Nation, Matthew A. Cooper, Sally E. Plush, Douglas A. Brooks, Frederick M. Pfeffer

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

23 Citations (Scopus)

Abstract

The design, synthesis and evaluation of a small series of potent amphiphilic norbornane antibacterial agents has been performed (compound 10 MIC = 0.25 μg/mL against MRSA). Molecular modelling indicates rapid aggregation of this class of antibacterial agent prior to membrane association and insertion. Two fluorescent analogues (compound 29 with 4-amino-naphthalimide and 34 with 4-nitrobenz-2-oxa-1,3-diazole fluorophores) with good activity (MIC = 0.5 μg/mL against MRSA) were also constructed and confocal microscopy studies indicate that the primary site of interaction for this family of compounds is the bacterial membrane.

Original language	English
Pages (from-to)	9-22
Number of pages	14
Journal	European Journal of Medicinal Chemistry
Volume	160
DOIs	https://doi.org/10.1016/j.ejmech.2018.09.072
Publication status	Published - 5 Dec 2018

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10.1016/j.ejmech.2018.09.072

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Hickey, S. M., Ashton, T. D., Boer, G., Bader, C. A., Thomas, M., Elliott, A. G., Schmuck, C., Yu, H. Y., Li, J., Nation, R. L., Cooper, M. A., Plush, S. E., Brooks, D. A., & Pfeffer, F. M. (2018). Norbornane-based cationic antimicrobial peptidomimetics targeting the bacterial membrane. European Journal of Medicinal Chemistry, 160, 9-22. https://doi.org/10.1016/j.ejmech.2018.09.072

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title = "Norbornane-based cationic antimicrobial peptidomimetics targeting the bacterial membrane",

abstract = "The design, synthesis and evaluation of a small series of potent amphiphilic norbornane antibacterial agents has been performed (compound 10 MIC = 0.25 μg/mL against MRSA). Molecular modelling indicates rapid aggregation of this class of antibacterial agent prior to membrane association and insertion. Two fluorescent analogues (compound 29 with 4-amino-naphthalimide and 34 with 4-nitrobenz-2-oxa-1,3-diazole fluorophores) with good activity (MIC = 0.5 μg/mL against MRSA) were also constructed and confocal microscopy studies indicate that the primary site of interaction for this family of compounds is the bacterial membrane.",

keywords = "Amphiphilic, Antibacterial, Antimicrobial, Fluorescence, Naphthalimide, Norbornane and microscopy",

author = "Hickey, {Shane M.} and Ashton, {Trent D.} and Gareth Boer and Bader, {Christie A.} and Michael Thomas and Elliott, {Alysha G.} and Carsten Schmuck and Yu, {Heidi Y.} and Jian Li and Nation, {Roger L.} and Cooper, {Matthew A.} and Plush, {Sally E.} and Brooks, {Douglas A.} and Pfeffer, {Frederick M.}",

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doi = "10.1016/j.ejmech.2018.09.072",

language = "English",

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T1 - Norbornane-based cationic antimicrobial peptidomimetics targeting the bacterial membrane

AU - Hickey, Shane M.

AU - Ashton, Trent D.

AU - Boer, Gareth

AU - Bader, Christie A.

AU - Thomas, Michael

AU - Elliott, Alysha G.

AU - Schmuck, Carsten

AU - Yu, Heidi Y.

AU - Li, Jian

AU - Nation, Roger L.

AU - Cooper, Matthew A.

AU - Plush, Sally E.

AU - Brooks, Douglas A.

AU - Pfeffer, Frederick M.

PY - 2018/12/5

Y1 - 2018/12/5

N2 - The design, synthesis and evaluation of a small series of potent amphiphilic norbornane antibacterial agents has been performed (compound 10 MIC = 0.25 μg/mL against MRSA). Molecular modelling indicates rapid aggregation of this class of antibacterial agent prior to membrane association and insertion. Two fluorescent analogues (compound 29 with 4-amino-naphthalimide and 34 with 4-nitrobenz-2-oxa-1,3-diazole fluorophores) with good activity (MIC = 0.5 μg/mL against MRSA) were also constructed and confocal microscopy studies indicate that the primary site of interaction for this family of compounds is the bacterial membrane.

AB - The design, synthesis and evaluation of a small series of potent amphiphilic norbornane antibacterial agents has been performed (compound 10 MIC = 0.25 μg/mL against MRSA). Molecular modelling indicates rapid aggregation of this class of antibacterial agent prior to membrane association and insertion. Two fluorescent analogues (compound 29 with 4-amino-naphthalimide and 34 with 4-nitrobenz-2-oxa-1,3-diazole fluorophores) with good activity (MIC = 0.5 μg/mL against MRSA) were also constructed and confocal microscopy studies indicate that the primary site of interaction for this family of compounds is the bacterial membrane.

KW - Amphiphilic

KW - Antibacterial

KW - Antimicrobial

KW - Fluorescence

KW - Naphthalimide

KW - Norbornane and microscopy

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U2 - 10.1016/j.ejmech.2018.09.072

DO - 10.1016/j.ejmech.2018.09.072

M3 - Article

SN - 0223-5234

VL - 160

SP - 9

EP - 22

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

ER -

Norbornane-based cationic antimicrobial peptidomimetics targeting the bacterial membrane

Abstract

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