Potential Anticancer Platinum-Ruthenium Complexes' Interaction with DNA and Their Affect on DNA Replication
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Treatment of cancer with chemotherapy drugs is typically harsh and not ideal. Patients may also develop resistance to a particular drug, therefore creating a need for new anticancer compounds. Platinum and ruthenium based drugs have the potential to be more effective at lower concentrations and also more specifically target cancer cells. AH- 197 and IT-127 are two novel, potential chemotheraputic agents, modeled after cisplatin, a commonly used chemotherapy drug, and NAMI-A, a ruthenium based compound that has exhibited selective anti-metastatic properties. Thus far, AH-197 and IT-127 have been chemically characterized and are being tested for their ability to inhibit cell motility and bind to various proteins. Cisplatin’s cytotoxicity can be attributed to its ability to form covalent bonds between adjacent guanines in DNA, distorting its helical structure, which inhibits DNA replication. Once a large degree of DNA replication has been inhibited, DNA repair pathways are activated and eventually apoptosis is induced. This research shows that AH197 and IT127 more effectively inhibit DNA replication in an in vitro experiment, than cisplatin at equivalent concentrations. An in vivo DNA replication assay also suggests that AH197 is capable of inhibiting more DNA replication than cisplatin in the COLO 205 cancer cell line. Preliminary experiments leading to the development of a protocol to determine if AH197 and IT127 preferentially bind to specific sequences of DNA have also been performed. These results suggest that AH197 and IT127 have the potential to be effective chemotherapy drugs.
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Schubert, Laura, "Potential Anticancer Platinum-Ruthenium Complexes' Interaction with DNA and Their Affect on DNA Replication" (2012). Senior Projects Spring 2012. 80.
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