Synthesis, anti-proliferative activity, and toxicity of C4(C5) substituted N,N′-bis(arylmethyl)imidazolium salts

Kerri L. Shelton; Michael A. DeBord; Patrick O. Wagers; Marie R. Southerland; Alexandra Taraboletti; Nikki K. Robishaw; Daniel P. Jackson; Radisa Tosanovic; William G. Kofron; Claire A. Tessier; Sailaja Paruchuri; Leah P. Shriver; Matthew J. Panzner; Wiley J. Youngs

doi:10.1016/j.tet.2016.07.068

Synthesis, anti-proliferative activity, and toxicity of C⁴(C⁵) substituted N,N′-bis(arylmethyl)imidazolium salts

Kerri L. Shelton, Michael A. DeBord, Patrick O. Wagers, Marie R. Southerland, Alexandra Taraboletti, Nikki K. Robishaw, Daniel P. Jackson, Radisa Tosanovic, William G. Kofron, Claire A. Tessier, Sailaja Paruchuri, Leah P. Shriver, Matthew J. Panzner, Wiley J. Youngs

Department of Chemistry

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

12 Scopus citations

Abstract

The syntheses and characterization of C⁴and C⁵substituted N,N′-bis(arylmethyl)imidazolium salts with hydrophilic or lipophilic substituents on the imidazole ring are reported. A structure-activity relationship study revealed that the lipophilicity of groups at the C⁴and C⁵positions plays a crucial role in modulating the efficacy against select non-small cell lung cancer cell lines tested. Compounds 11–17 were determined to be the most active against the panel of cell lines studied. Compounds 11 and 12 were examined by the National Cancer Institute's Developmental Therapeutic Program where they were tested against the NCI-60 human cancer cell line panel in a one-dose and five-dose assay. Compound 11 had high activity against the nine lung cancer lines tested while 12 had cytotoxic effects against 59 of the 60 cell lines. Compound 11 was also studied in a murine model to determine its in vivo toxicity.

Original language	English
Pages (from-to)	5729-5743
Number of pages	15
Journal	Tetrahedron
Volume	72
Issue number	38
DOIs	https://doi.org/10.1016/j.tet.2016.07.068
State	Published - 2016

Keywords

Anti-proliferative
Anti-tumor
Imidazolium salt
Lung cancer

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Shelton, K. L., DeBord, M. A., Wagers, P. O., Southerland, M. R., Taraboletti, A., Robishaw, N. K., Jackson, D. P., Tosanovic, R., Kofron, W. G., Tessier, C. A., Paruchuri, S., Shriver, L. P., Panzner, M. J., & Youngs, W. J. (2016). Synthesis, anti-proliferative activity, and toxicity of C⁴(C⁵) substituted N,N′-bis(arylmethyl)imidazolium salts. Tetrahedron, 72(38), 5729-5743. https://doi.org/10.1016/j.tet.2016.07.068

@article{bb9e8215cfdf4b758ff795d364b97a5c,

title = "Synthesis, anti-proliferative activity, and toxicity of C4(C5) substituted N,N′-bis(arylmethyl)imidazolium salts",

abstract = "The syntheses and characterization of C4and C5substituted N,N′-bis(arylmethyl)imidazolium salts with hydrophilic or lipophilic substituents on the imidazole ring are reported. A structure-activity relationship study revealed that the lipophilicity of groups at the C4and C5positions plays a crucial role in modulating the efficacy against select non-small cell lung cancer cell lines tested. Compounds 11–17 were determined to be the most active against the panel of cell lines studied. Compounds 11 and 12 were examined by the National Cancer Institute's Developmental Therapeutic Program where they were tested against the NCI-60 human cancer cell line panel in a one-dose and five-dose assay. Compound 11 had high activity against the nine lung cancer lines tested while 12 had cytotoxic effects against 59 of the 60 cell lines. Compound 11 was also studied in a murine model to determine its in vivo toxicity.",

keywords = "Anti-proliferative, Anti-tumor, Imidazolium salt, Lung cancer",

author = "Shelton, {Kerri L.} and DeBord, {Michael A.} and Wagers, {Patrick O.} and Southerland, {Marie R.} and Alexandra Taraboletti and Robishaw, {Nikki K.} and Jackson, {Daniel P.} and Radisa Tosanovic and Kofron, {William G.} and Tessier, {Claire A.} and Sailaja Paruchuri and Shriver, {Leah P.} and Panzner, {Matthew J.} and Youngs, {Wiley J.}",

note = "Publisher Copyright: {\textcopyright} 2016",

year = "2016",

doi = "10.1016/j.tet.2016.07.068",

language = "English",

volume = "72",

pages = "5729--5743",

journal = "Tetrahedron",

issn = "0040-4020",

number = "38",

}

Shelton, KL, DeBord, MA, Wagers, PO, Southerland, MR, Taraboletti, A, Robishaw, NK, Jackson, DP, Tosanovic, R, Kofron, WG, Tessier, CA, Paruchuri, S, Shriver, LP, Panzner, MJ & Youngs, WJ 2016, 'Synthesis, anti-proliferative activity, and toxicity of C⁴(C⁵) substituted N,N′-bis(arylmethyl)imidazolium salts', Tetrahedron, vol. 72, no. 38, pp. 5729-5743. https://doi.org/10.1016/j.tet.2016.07.068

TY - JOUR

T1 - Synthesis, anti-proliferative activity, and toxicity of C4(C5) substituted N,N′-bis(arylmethyl)imidazolium salts

AU - Shelton, Kerri L.

AU - DeBord, Michael A.

AU - Wagers, Patrick O.

AU - Southerland, Marie R.

AU - Taraboletti, Alexandra

AU - Robishaw, Nikki K.

AU - Jackson, Daniel P.

AU - Tosanovic, Radisa

AU - Kofron, William G.

AU - Tessier, Claire A.

AU - Paruchuri, Sailaja

AU - Shriver, Leah P.

AU - Panzner, Matthew J.

AU - Youngs, Wiley J.

PY - 2016

Y1 - 2016

N2 - The syntheses and characterization of C4and C5substituted N,N′-bis(arylmethyl)imidazolium salts with hydrophilic or lipophilic substituents on the imidazole ring are reported. A structure-activity relationship study revealed that the lipophilicity of groups at the C4and C5positions plays a crucial role in modulating the efficacy against select non-small cell lung cancer cell lines tested. Compounds 11–17 were determined to be the most active against the panel of cell lines studied. Compounds 11 and 12 were examined by the National Cancer Institute's Developmental Therapeutic Program where they were tested against the NCI-60 human cancer cell line panel in a one-dose and five-dose assay. Compound 11 had high activity against the nine lung cancer lines tested while 12 had cytotoxic effects against 59 of the 60 cell lines. Compound 11 was also studied in a murine model to determine its in vivo toxicity.

AB - The syntheses and characterization of C4and C5substituted N,N′-bis(arylmethyl)imidazolium salts with hydrophilic or lipophilic substituents on the imidazole ring are reported. A structure-activity relationship study revealed that the lipophilicity of groups at the C4and C5positions plays a crucial role in modulating the efficacy against select non-small cell lung cancer cell lines tested. Compounds 11–17 were determined to be the most active against the panel of cell lines studied. Compounds 11 and 12 were examined by the National Cancer Institute's Developmental Therapeutic Program where they were tested against the NCI-60 human cancer cell line panel in a one-dose and five-dose assay. Compound 11 had high activity against the nine lung cancer lines tested while 12 had cytotoxic effects against 59 of the 60 cell lines. Compound 11 was also studied in a murine model to determine its in vivo toxicity.

KW - Anti-proliferative

KW - Anti-tumor

KW - Imidazolium salt

KW - Lung cancer

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U2 - 10.1016/j.tet.2016.07.068

DO - 10.1016/j.tet.2016.07.068

M3 - Article

AN - SCOPUS:84981731273

SN - 0040-4020

VL - 72

SP - 5729

EP - 5743

JO - Tetrahedron

JF - Tetrahedron

IS - 38

ER -

Synthesis, anti-proliferative activity, and toxicity of C⁴(C⁵) substituted N,N′-bis(arylmethyl)imidazolium salts

Abstract

Keywords

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