Synthesis, characterization, and biological activity of a triphenylphosphonium-containing imidazolium salt against select bladder cancer cell lines

Philip H. Abbosh; Michael L. Stromyer; Marie R. Southerland; Uttam Satyal; Rahmat K. Sikder; David J. Weader; Jessi A. Baughman; Wiley J. Youngs

doi:10.1016/j.ejmech.2019.111832

Synthesis, characterization, and biological activity of a triphenylphosphonium-containing imidazolium salt against select bladder cancer cell lines

Philip H. Abbosh, Michael L. Stromyer, Marie R. Southerland, Uttam Satyal, Rahmat K. Sikder, David J. Weader, Jessi A. Baughman, Wiley J. Youngs

Nuclear Dynamics and Cancer (NDC)

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

15 Scopus citations

Abstract

Imidazolium salts have shown great promise as anticancer materials. A new imidazolium salt (TPP1), with a triphenylphosphonium substituent, has been synthesized and evaluated for in vitro and in vivo cytotoxicity against bladder cancer. TPP1 was determined to have a GI₅₀ ranging from 200 to 250 μM over a period of 1 h and the ability to effectively inhibit bladder cancer. TPP1 induces apoptosis, and it appears to act as a direct mitochondrial toxin. TPP1 was applied intravesically to a bladder cancer mouse model based on the carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Cancer selectivity of TPP1 was demonstrated, as BBN-induced tumors exhibited apoptosis but normal adjacent urothelium did not. These results suggest that TPP1 may be a promising intravesical agent for the treatment of bladder cancer.

Original language	English
Article number	111832
Pages (from-to)	111832
Journal	European Journal of Medicinal Chemistry
Volume	185
DOIs	https://doi.org/10.1016/j.ejmech.2019.111832
State	Published - Jan 1 2020

Keywords

Animals
Antineoplastic Agents/chemical synthesis
Cell Line, Tumor
Cell Proliferation/drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Female
Humans
Imidazoles/chemical synthesis
Male
Mice
Models, Molecular
Molecular Structure
Neoplasms, Experimental/drug therapy
Organophosphorus Compounds/chemical synthesis
Structure-Activity Relationship
Urinary Bladder Neoplasms/drug therapy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ejmech.2019.111832

Cite this

Abbosh, P. H., Stromyer, M. L., Southerland, M. R., Satyal, U., Sikder, R. K., Weader, D. J., Baughman, J. A., & Youngs, W. J. (2020). Synthesis, characterization, and biological activity of a triphenylphosphonium-containing imidazolium salt against select bladder cancer cell lines. European Journal of Medicinal Chemistry, 185, 111832. Article 111832. https://doi.org/10.1016/j.ejmech.2019.111832

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title = "Synthesis, characterization, and biological activity of a triphenylphosphonium-containing imidazolium salt against select bladder cancer cell lines",

abstract = "Imidazolium salts have shown great promise as anticancer materials. A new imidazolium salt (TPP1), with a triphenylphosphonium substituent, has been synthesized and evaluated for in vitro and in vivo cytotoxicity against bladder cancer. TPP1 was determined to have a GI50 ranging from 200 to 250 μM over a period of 1 h and the ability to effectively inhibit bladder cancer. TPP1 induces apoptosis, and it appears to act as a direct mitochondrial toxin. TPP1 was applied intravesically to a bladder cancer mouse model based on the carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Cancer selectivity of TPP1 was demonstrated, as BBN-induced tumors exhibited apoptosis but normal adjacent urothelium did not. These results suggest that TPP1 may be a promising intravesical agent for the treatment of bladder cancer.",

keywords = "Animals, Antineoplastic Agents/chemical synthesis, Cell Line, Tumor, Cell Proliferation/drug effects, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Female, Humans, Imidazoles/chemical synthesis, Male, Mice, Models, Molecular, Molecular Structure, Neoplasms, Experimental/drug therapy, Organophosphorus Compounds/chemical synthesis, Structure-Activity Relationship, Urinary Bladder Neoplasms/drug therapy",

author = "Abbosh, {Philip H.} and Stromyer, {Michael L.} and Southerland, {Marie R.} and Uttam Satyal and Sikder, {Rahmat K.} and Weader, {David J.} and Baughman, {Jessi A.} and Youngs, {Wiley J.}",

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier Masson SAS",

year = "2020",

month = jan,

day = "1",

doi = "10.1016/j.ejmech.2019.111832",

language = "English",

volume = "185",

pages = "111832",

journal = "European Journal of Medicinal Chemistry",

issn = "0223-5234",

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Abbosh, PH, Stromyer, ML, Southerland, MR, Satyal, U, Sikder, RK, Weader, DJ, Baughman, JA & Youngs, WJ 2020, 'Synthesis, characterization, and biological activity of a triphenylphosphonium-containing imidazolium salt against select bladder cancer cell lines', European Journal of Medicinal Chemistry, vol. 185, 111832, pp. 111832. https://doi.org/10.1016/j.ejmech.2019.111832

Synthesis, characterization, and biological activity of a triphenylphosphonium-containing imidazolium salt against select bladder cancer cell lines. / Abbosh, Philip H.; Stromyer, Michael L.; Southerland, Marie R. et al.
In: European Journal of Medicinal Chemistry, Vol. 185, 111832, 01.01.2020, p. 111832.

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

TY - JOUR

T1 - Synthesis, characterization, and biological activity of a triphenylphosphonium-containing imidazolium salt against select bladder cancer cell lines

AU - Abbosh, Philip H.

AU - Stromyer, Michael L.

AU - Southerland, Marie R.

AU - Satyal, Uttam

AU - Sikder, Rahmat K.

AU - Weader, David J.

AU - Baughman, Jessi A.

AU - Youngs, Wiley J.

PY - 2020/1/1

Y1 - 2020/1/1

N2 - Imidazolium salts have shown great promise as anticancer materials. A new imidazolium salt (TPP1), with a triphenylphosphonium substituent, has been synthesized and evaluated for in vitro and in vivo cytotoxicity against bladder cancer. TPP1 was determined to have a GI50 ranging from 200 to 250 μM over a period of 1 h and the ability to effectively inhibit bladder cancer. TPP1 induces apoptosis, and it appears to act as a direct mitochondrial toxin. TPP1 was applied intravesically to a bladder cancer mouse model based on the carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Cancer selectivity of TPP1 was demonstrated, as BBN-induced tumors exhibited apoptosis but normal adjacent urothelium did not. These results suggest that TPP1 may be a promising intravesical agent for the treatment of bladder cancer.

AB - Imidazolium salts have shown great promise as anticancer materials. A new imidazolium salt (TPP1), with a triphenylphosphonium substituent, has been synthesized and evaluated for in vitro and in vivo cytotoxicity against bladder cancer. TPP1 was determined to have a GI50 ranging from 200 to 250 μM over a period of 1 h and the ability to effectively inhibit bladder cancer. TPP1 induces apoptosis, and it appears to act as a direct mitochondrial toxin. TPP1 was applied intravesically to a bladder cancer mouse model based on the carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Cancer selectivity of TPP1 was demonstrated, as BBN-induced tumors exhibited apoptosis but normal adjacent urothelium did not. These results suggest that TPP1 may be a promising intravesical agent for the treatment of bladder cancer.

KW - Animals

KW - Antineoplastic Agents/chemical synthesis

KW - Cell Line, Tumor

KW - Cell Proliferation/drug effects

KW - Dose-Response Relationship, Drug

KW - Drug Screening Assays, Antitumor

KW - Female

KW - Humans

KW - Imidazoles/chemical synthesis

KW - Male

KW - Mice

KW - Models, Molecular

KW - Molecular Structure

KW - Neoplasms, Experimental/drug therapy

KW - Organophosphorus Compounds/chemical synthesis

KW - Structure-Activity Relationship

KW - Urinary Bladder Neoplasms/drug therapy

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U2 - 10.1016/j.ejmech.2019.111832

DO - 10.1016/j.ejmech.2019.111832

M3 - Article

C2 - 31718944

SN - 0223-5234

VL - 185

SP - 111832

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

M1 - 111832

ER -

Synthesis, characterization, and biological activity of a triphenylphosphonium-containing imidazolium salt against select bladder cancer cell lines

Abstract

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Synthesis, characterization, and biological activity of a triphenylphosphonium-containing imidazolium salt against select bladder cancer cell lines

Abstract

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UN SDGs

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