Award Date

1-1-2005

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Chemistry

First Committee Member

Stephen W. Carper

Number of Pages

101

Abstract

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.

Keywords

Analogs; Breast; Cells; Characterization; Cisplating; Cytotoxicity; Novel; Synthesis

Controlled Subject

Biochemistry

File Format

pdf

File Size

2693.12 KB

Degree Grantor

University of Nevada, Las Vegas

Language

English

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