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VCU Massey Cancer Center researchers identify a new class of anti-cancer drugs based on platinum

Researchers at Virginia Commonwealth University's Massey Cancer Center have created a new platinum-based, anti-cancer agent able to overcome acquired drug resistance by first modifying the way it is absorbed into cancer cells and then attacking the DNA of those cancer cells.

The findings may help researchers design a new generation of anti-cancer drugs that selectively target cancer cells, reduce resistance and side effects and expand the range of tumors that can be treated by platinum.

In the Dec. 26 issue of the journal Inorganic Chemistry researchers reported on the design of a new trinuclear platinum compound and demonstrated that its cellular absorption is significantly greater than that of neutral cisplatin, as well as other multi-nuclear platinum compounds. The enhanced uptake into cancer cells takes advantage of weak molecular interactions on the cells' surface. These results underscore the importance of the new compound's "non-covalent" interactions, prior to the attack on DNA. Non-covalent interactions minimize potential side reactions and produce changes in the structure of proteins and DNA, which is different from currently used drugs. This research was selected as the cover article for the print version of the journal, Issue 26.

Researchers compared the cytotoxicity and cellular concentrations of three anti-cancer drugs including the phase II clinical drug, BBR 3464, cisplatin and the new trinuclear platinum compound. In a laboratory model, human ovarian cancer cells were exposed to each drug.

"In platinum antitumor chemistry our objective is to design and develop complexes acting by new mechanisms of action," said Nicholas Farrell, Ph.D., professor and chair in the Department of Chemistry at VCU, and lead author of the study. "Resistance to current drugs is due to poor cellular absorption and an increased ability of the cell to process or repair the damage caused by the chemotherapeutic agent."

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Source:Virginia Commonwealth University


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