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Rational Design and Anti-proliferative Activity Of Substituted N,N'- bis(arylmethyl)imidazolium Salts as Varied Therapeutics

Taylor, Kerri Shelton
http://orcid.org/0000-0001-6034-7581
http://rave.ohiolink.edu/etdc/view?acc_num=akron1461063089

Abstract Details

2016, Doctor of Philosophy, University of Akron, Chemistry.
Imidazolium salts are unique for their biological activity and application in the field of cancer research. Pharmaceutical research of imidazole-based antitumor compounds has led to the identification of highly effective N,N’-substituted imidazolium salts with comparable activity to that of cisplatin, which has been used as a chemotherapeutic agent for decades. The high toxicity of present cancer treatments has prompted the investigation into other compounds with similar efficacy. Select N,N’-bis(arylmethyl)-imidazolium salts have been shown to exhibit high anti-proliferative activity, yet these compounds have inferior aqueous solubilities. This dissertation describes the rational design and biological activity of N,N’-bis(arylmethyl)imidazolium salts with hydrophilic and hydrophobic substituents on the imidazole ring for the treatment of lung carcinomas and chronic urinary tract infections. Chapter I discusses the background and development of N,N’-substituted imidazolium salts within the field of antitumor research. Chapter II addresses the synthesis and anti-proliferative activity of C4(C5) substituted N,N’-bis(arylmethyl)-imidazolium salts with hydrophilic or lipophilic groups on the imidazole ring. In vitro activity of these seventeen imidazolium salts against select non-small cell lung cancer cell (NSCLC) lines (NCI-H460, HCC827, and NCI-H1975) was analyzed by biological assays. It was determined that the phenyl substituents at the C4(C5) positions increased the in vitro antitumor activity of these salts to create highly active compounds. Chapter III is designated to the synthesis and anti-proliferative activity of thirty-one N,N’-bis(arylmethyl)benzimidazolium salts against NCI-H460, HCC827, NCI-H1975, and NCI-A549 lung cancer cell lines. Our data confirms that naphthylmethyl substituents at the nitrogen atoms (N1(N3)) and highly lipophilic substituents at the carbon atoms (C2 and C5(C6)) can generate benzimidazolium salts with anti-proliferative activity comparable to that of cisplatin. Chapter IV focuses on a unique set of imidazolium salts as small molecule bladder exfoliants. Protamine sulfate is presently used in clinical studies for its exfoliative properties, yet the material has disadvantages in the form of adverse reactions and injury of bladder tissue. Results from in vitro and in vivo models showed that select imidazolium salts were highly potent in treating the recurring Escherichia coli. Chapter V outlines the structure activity relationship between substituents and compound efficacy of N,N’-substituted imidazolium salts.
Wiley Youngs, Dr. (Advisor)
Claire Tessier, Dr. (Committee Member)
Chrys Wesdemiotis, Dr. (Committee Member)
David Modarelli, Dr. (Committee Member)
Yang Yun, Dr. (Committee Member)
523 p.
Chemistry
Antitumor, Lung cancer, Non-Small Cell Lung Cancer, Imidazolium salt, Benzimidazolium salt

Recommended Citations

Citations

  • Taylor, K. S. (2016). Rational Design and Anti-proliferative Activity Of Substituted N,N'- bis(arylmethyl)imidazolium Salts as Varied Therapeutics [Doctoral dissertation, University of Akron]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=akron1461063089

    APA Style (7th edition)

  • Taylor, Kerri. Rational Design and Anti-proliferative Activity Of Substituted N,N'- bis(arylmethyl)imidazolium Salts as Varied Therapeutics. 2016. University of Akron, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=akron1461063089.

    MLA Style (8th edition)

  • Taylor, Kerri. "Rational Design and Anti-proliferative Activity Of Substituted N,N'- bis(arylmethyl)imidazolium Salts as Varied Therapeutics." Doctoral dissertation, University of Akron, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=akron1461063089

    Chicago Manual of Style (17th edition)

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© 2016, all rights reserved.
This open access ETD is published by University of Akron and OhioLINK.