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
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.
"In platinum antitumor chemistry our objective is to design and develop complexes acting by new mechanisms of action. 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," Nicholas Farrell, Ph.D., professor and lead author of the study, said.
"The effectiveness of a platinum drug in killing cells is directly related to its concentration inside the cell," he added
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