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Synthesis, characterization, and anti-cancer structure-activity relationship studies of imidazolium salts

DeBord, Michael
http://rave.ohiolink.edu/etdc/view?acc_num=akron1489414733025495

Abstract Details

2017, Doctor of Philosophy, University of Akron, Chemistry.
Imidazolium salts have received significant attention for their anti-cancer properties. Human cancer cell lines have been treated with hundreds of imidazolium salts and many have shown promise for clinical potential. The leader of this class is YM155, a survivin suppressor that has gone through clinical trials but is not yet approved by the Food and Drug Administration (FDA) for the treatment of cancer. Numerous studies have been compiled to create structure activity relationships addressing what functional groups can help increase anti-proliferative effects and which functional groups produce imidazolium salts with weak anti-cancer properties. The general trend throughout the literature is that lipophilicity increases anti-cancer potential. Unfortunately, little is known about the mechanism of action, cellular target, and specificity of imidazolium salts which are all limiting factors towards progression into clinical applications. Chapter II describes the synthesis and characterization of a series of N,N’-bis(naphthylmethyl) imidazolium salts. These compounds were also tested for their in vitro anti-cancer properties against several non-small cell lung cancer cell lines and found to be highly active. Each compound had low aqueous solubility, but could be solubilized by a cyclodextrin that is FDA approved for drug formulations. In vitro mechanism of action studies were also performed on one compound and suggested the compound induced an apoptotic mode of cell death. Chapter III provides the synthesis and characterization of a related series of compounds with higher aqueous solubility. The major findings included the incorporation of quinolylmethyl moieties, similar to naphthylmethyl substituents, to increase aqueous solubility without drastically lowering anti-cancer activity. It was also determined that the anion plays a significant role in the aqueous solubility of these imidazolium salts. Chapter IV presents the synthesis, characterization, and in vitro analysis of a series of bis-imidazolium salts. Each of these compounds has two positively charged imidazole rings to increase the hydrophilic nature compared to other lipophilic derivatives. These compounds follow trends found in the literature concerning their structure-activity relationships: enhanced lipophilicity produces compounds with higher in vitro anti-cancer activity. Chapter V provides concluding remarks.
Wiley Youngs, Dr. (Advisor)
Claire Tessier, Dr. (Committee Member)
Ziegler Chris, Dr. (Committee Member)
Shriver Leah, Dr. (Committee Member)
Hossein Tavana (Committee Member)
287 p.
Biochemistry; Chemistry; Medicine
imidazolium salt; anti-cancer; anti-tumor; lung cancer; cyclodextrin; non-small cell lung cancer; naphthalene; quinoline

Recommended Citations

Citations

  • DeBord, M. (2017). Synthesis, characterization, and anti-cancer structure-activity relationship studies of imidazolium salts [Doctoral dissertation, University of Akron]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=akron1489414733025495

    APA Style (7th edition)

  • DeBord, Michael. Synthesis, characterization, and anti-cancer structure-activity relationship studies of imidazolium salts. 2017. University of Akron, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=akron1489414733025495.

    MLA Style (8th edition)

  • DeBord, Michael. "Synthesis, characterization, and anti-cancer structure-activity relationship studies of imidazolium salts." Doctoral dissertation, University of Akron, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=akron1489414733025495

    Chicago Manual of Style (17th edition)

akron1489414733025495
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© 2017, all rights reserved.
This open access ETD is published by University of Akron and OhioLINK.