Effects of Cisplatin Analog Size on the Reaction with DNA Bases

<p>Cancer is the second leading cause of death in the United States. Cisplatin is one of the well-known anti-cancer agents used to treat testicular and ovarian cancers. It mainly binds to the DNA bases, which leads to cell death. The cytotoxic activity of the cisplatin analogs is due to the interaction of platinum with nucleotides like adenine at N₇ or N₁ position and guanine at N₇ position. Guanine is the primary target for cisplatin analogs whereas adenine is the secondary target. Cisplatin analogs, [Pt(Me₅dien)(D₂O)]²⁺[Me₅dien = N,N,N’,N’,N’’-pentamethyl diethylene triamine] and [Pt(dien)(D₂O)]²⁺[dien=diethylene triamine] were synthesized and their effects on AMP and GMP were studied using NMR spectroscopy. The experiments were conducted to examine the effects of bulk on 5’-GMP and 5’-AMP. The results suggest that bulk slows down the reaction with AMP more than with that of GMP. The order of reactivity is Pt(dien)(GMP)> Pt(dien)(AMP) > Pt(Me₅dien)(GMP) > Pt(Me₅dien)(AMP). The reaction of the [Pt(Me₅dien)(D₂O)]²⁺ complex with AMP leads to multiple products, some of which appear to be due to coordination at N₁ instead of N₇.</p>

Name thesis:degree_name

Master of Science

Discipline thesis:degree_discipline

Department of Chemistry

Year

2013

Author dc:creator

• Nandala, Swathi

Contributors dc:contributor

• Kevin M. Williams (Director), Hemali Rathnayake, Bangbo Yan

• Adenine
• Platinum
• Guanine
• Nuclear Magnetic Resonance (NMR) Spectroscopy
• Heteronuclear Multiple Quantum Coherence (HMQC) Spectroscopy
• Chemotherapy
• Chemistry-Organic
• Spectrum Analysis
• Chemistry
• Medicinal-Pharmaceutical Chemistry
• Organic Chemistry

Repository record dc:identifier

https://digitalcommons.wku.edu/theses/1256

OAI identifier oai:identifier

oai:digitalcommons.wku.edu:theses-2259