Novel Photodissociable Ruthenium-Based Anticancer Drugs
Start date: Jul 1, 2008,
End date: Jun 30, 2010
"The discovery of cisplatin, cis-diamminedichloroplatinum(II), as an anticancer drug is a landmark of modern inorganic medicinal chemistry. Platinum drugs are the best-selling antitumor drugs in the world and they are effective in treating a variety of cancers. During the last decade, the search for new anticancer compounds has been widened to other transition metals. Ruthenium complexes in particular have shown considerable promise because of their rich synthetic chemistry, the range of oxidation states, the common octahedral geometry, and finally also because of their rich photochemistry. The fundamental goal of this project is to investigate the possibility of developing new types of hybrid ruthenium-based chemotherapeutic drugs that can be activated by irradiation with low-energy light. When irradiated these molecules form reactive aqua species and, at the same time, release biologically active ligands. The ligands can interfere with the cell cycle at a number of targets, while the metal-containing aqua species inhibit mitosis by binding to DNA. The proposed approach can lead to development of milder, more specific, and tunable drugs which can decrease the negative side-effects of chemotherapy. Inorganic and organic synthetic methodologies, advanced spectroscopic and analytical techniques will be used together with biochemical and medical methods to pursue the objectives of the project. The multi- and interdisciplinary nature of the research will prompt the applicant to acquire practical and theoretical skills on chemical biology and medical chemistry, to improve his independent thinking and leadership qualities, enhancing his scientific competencies and helping the applicant to attain an independent position."
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