Synthesis, characterization, in vitro SAR study, and preliminary in vivo toxicity evaluation of naphthylmethyl substituted bis-imidazolium salts

Marie R. Southerland; Michael A. DeBord; Nicholas A. Johnson; Steven R. Crabtree; Nicolas E. Alexander; Michael L. Stromyer; Patrick O. Wagers; Matthew J. Panzner; Chrys Wesdemiotis; Leah P. Shriver; Claire A. Tessier; Wiley J. Youngs

doi:10.1016/j.bmc.2020.115893

Synthesis, characterization, in vitro SAR study, and preliminary in vivo toxicity evaluation of naphthylmethyl substituted bis-imidazolium salts

Marie R. Southerland
, Michael A. DeBord
, Nicholas A. Johnson
, Steven R. Crabtree
, Nicolas E. Alexander
, Michael L. Stromyer
, Patrick O. Wagers
, Matthew J. Panzner
, Chrys Wesdemiotis
, Leah P. Shriver
, Claire A. Tessier
, Wiley J. Youngs

Department of Chemistry

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

3 Scopus citations

Abstract

A series of novel bis-imidazolium salts was synthesized, characterized, and evaluated in vitro against a panel of non-small cell lung cancer (NSCLC) cells. Two imidazolium cores were connected with alkyl chains of varying lengths to develop a structure activity relationship (SAR). Increasing the length of the connecting alkyl chain was shown to correlate to an increase in the anti-proliferative activity. The National Cancer Institute's NCI-60 human tumor cell line screen confirmed this trend. The compound containing a decyl linker chain, 10, was chosen for further in vivo toxicity studies with C578BL/6 mice. The compound was well tolerated by the mice and all of the animals survived and gained weight over the course of the study.

Original language	English
Article number	115893
Journal	Bioorganic and Medicinal Chemistry
Volume	30
DOIs	https://doi.org/10.1016/j.bmc.2020.115893
State	Published - Jan 15 2021

Keywords

Bis-imidazolium salt
Imidazolium salt
In vivo toxicity
Non-small cell lung cancer
SAR

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10.1016/j.bmc.2020.115893

Cite this

Southerland, M. R., DeBord, M. A., Johnson, N. A., Crabtree, S. R., Alexander, N. E., Stromyer, M. L., Wagers, P. O., Panzner, M. J., Wesdemiotis, C., Shriver, L. P., Tessier, C. A., & Youngs, W. J. (2021). Synthesis, characterization, in vitro SAR study, and preliminary in vivo toxicity evaluation of naphthylmethyl substituted bis-imidazolium salts. Bioorganic and Medicinal Chemistry, 30, Article 115893. https://doi.org/10.1016/j.bmc.2020.115893

@article{589e645f1e864aeaaf4ee96094590dc3,

title = "Synthesis, characterization, in vitro SAR study, and preliminary in vivo toxicity evaluation of naphthylmethyl substituted bis-imidazolium salts",

abstract = "A series of novel bis-imidazolium salts was synthesized, characterized, and evaluated in vitro against a panel of non-small cell lung cancer (NSCLC) cells. Two imidazolium cores were connected with alkyl chains of varying lengths to develop a structure activity relationship (SAR). Increasing the length of the connecting alkyl chain was shown to correlate to an increase in the anti-proliferative activity. The National Cancer Institute's NCI-60 human tumor cell line screen confirmed this trend. The compound containing a decyl linker chain, 10, was chosen for further in vivo toxicity studies with C578BL/6 mice. The compound was well tolerated by the mice and all of the animals survived and gained weight over the course of the study.",

keywords = "Bis-imidazolium salt, Imidazolium salt, In vivo toxicity, Non-small cell lung cancer, SAR",

author = "Southerland, \{Marie R.\} and DeBord, \{Michael A.\} and Johnson, \{Nicholas A.\} and Crabtree, \{Steven R.\} and Alexander, \{Nicolas E.\} and Stromyer, \{Michael L.\} and Wagers, \{Patrick O.\} and Panzner, \{Matthew J.\} and Chrys Wesdemiotis and Shriver, \{Leah P.\} and Tessier, \{Claire A.\} and Youngs, \{Wiley J.\}",

note = "Publisher Copyright: {\textcopyright} 2020",

year = "2021",

month = jan,

day = "15",

doi = "10.1016/j.bmc.2020.115893",

language = "English",

volume = "30",

journal = "Bioorganic and Medicinal Chemistry",

issn = "0968-0896",

}

Southerland, MR, DeBord, MA, Johnson, NA, Crabtree, SR, Alexander, NE, Stromyer, ML, Wagers, PO, Panzner, MJ, Wesdemiotis, C, Shriver, LP, Tessier, CA & Youngs, WJ 2021, 'Synthesis, characterization, in vitro SAR study, and preliminary in vivo toxicity evaluation of naphthylmethyl substituted bis-imidazolium salts', Bioorganic and Medicinal Chemistry, vol. 30, 115893. https://doi.org/10.1016/j.bmc.2020.115893

TY - JOUR

T1 - Synthesis, characterization, in vitro SAR study, and preliminary in vivo toxicity evaluation of naphthylmethyl substituted bis-imidazolium salts

AU - Southerland, Marie R.

AU - DeBord, Michael A.

AU - Johnson, Nicholas A.

AU - Crabtree, Steven R.

AU - Alexander, Nicolas E.

AU - Stromyer, Michael L.

AU - Wagers, Patrick O.

AU - Panzner, Matthew J.

AU - Wesdemiotis, Chrys

AU - Shriver, Leah P.

AU - Tessier, Claire A.

AU - Youngs, Wiley J.

PY - 2021/1/15

Y1 - 2021/1/15

N2 - A series of novel bis-imidazolium salts was synthesized, characterized, and evaluated in vitro against a panel of non-small cell lung cancer (NSCLC) cells. Two imidazolium cores were connected with alkyl chains of varying lengths to develop a structure activity relationship (SAR). Increasing the length of the connecting alkyl chain was shown to correlate to an increase in the anti-proliferative activity. The National Cancer Institute's NCI-60 human tumor cell line screen confirmed this trend. The compound containing a decyl linker chain, 10, was chosen for further in vivo toxicity studies with C578BL/6 mice. The compound was well tolerated by the mice and all of the animals survived and gained weight over the course of the study.

AB - A series of novel bis-imidazolium salts was synthesized, characterized, and evaluated in vitro against a panel of non-small cell lung cancer (NSCLC) cells. Two imidazolium cores were connected with alkyl chains of varying lengths to develop a structure activity relationship (SAR). Increasing the length of the connecting alkyl chain was shown to correlate to an increase in the anti-proliferative activity. The National Cancer Institute's NCI-60 human tumor cell line screen confirmed this trend. The compound containing a decyl linker chain, 10, was chosen for further in vivo toxicity studies with C578BL/6 mice. The compound was well tolerated by the mice and all of the animals survived and gained weight over the course of the study.

KW - Bis-imidazolium salt

KW - Imidazolium salt

KW - In vivo toxicity

KW - Non-small cell lung cancer

KW - SAR

UR - https://www.scopus.com/pages/publications/85098185275

U2 - 10.1016/j.bmc.2020.115893

DO - 10.1016/j.bmc.2020.115893

M3 - Article

C2 - 33333447

AN - SCOPUS:85098185275

SN - 0968-0896

VL - 30

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

M1 - 115893

ER -

Synthesis, characterization, in vitro SAR study, and preliminary in vivo toxicity evaluation of naphthylmethyl substituted bis-imidazolium salts

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Keywords

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