Master of Science (MS)
First Committee Member
Stephen W. Carper
Number of Pages
Cis-diamminedichloroplatinum (II) (cisplatin) has been used for three decades as an anti-cancer treatment, but is limited in its therapeutic uses by side effects and cell resistance. In this study, new cisplatin analogues were developed, synthesized, and evaluated for cytotoxicity and cellular mechanisms. Two novel drugs 4,4'-bis(4,4,4-trifluorobutyl)-2,2'-bipyridine-PtCl 2 and 4,4'-bis(4,4,4-trifluorobutyl)-2,2'-bipyridine-Re(CO)3Cl and two previously synthesized drugs 4,4'-dimethyl-2,2'-bipyridine-PtCl 2 and 4,4'-dimethyl-2,2'-bipyridine-Re(CO)3Cl were tested, in breast cancer cell lines MDA-MB-435, MDA-MB-231 and transformed cell lines DC4 and DB46. Cytotoxicity assays found that the rhenium-containing compounds had no effect in the transformed lines and the platinum compounds were more effective than cisplatin at inducing cell death in all cell lines. Flow cytometry revealed that the platinum compounds arrest cells at a different phase of the cell cycle than cisplatin. Differential fluorescent microscopy demonstrated that 4,4'-bis(4,4,4-trifluorobutyl)-2,2'-bipyridine-PtCl2 and 4,4'-dimethyl-2,2'-bipyridine-PtCl 2 induce programmed cell death through apoptotic and necrotic pathways; A patent has been applied for 4,4'-bis(4,4,4-trifluorobutyl)-2,2'-bipyridine-PtCl 2.
Analogs; Breast; Cells; Characterization; Cisplating; Cytotoxicity; Novel; Synthesis
University of Nevada, Las Vegas
If you are the rightful copyright holder of this dissertation or thesis and wish to have the full text removed from Digital Scholarship@UNLV, please submit a request to email@example.com and include clear identification of the work, preferably with URL.
Elwell, Kyler Elizabeth, "Novel cisplating analogs: Synthesis, characterization and cytotoxicity in breast cells" (2005). UNLV Retrospective Theses & Dissertations. 1826.
IN COPYRIGHT. For more information about this rights statement, please visit http://rightsstatements.org/vocab/InC/1.0/