The two copper ions bind precisely to two phosphates on DNA.
Image credit: Bielefeld University
The design of the new molecule is the work of chemists, biochemists and physicists from Bielefeld University in Germany who report their work in the journal Inorganic Chemistry.
The team, led by Thorsten Glaser, professor in inorganic chemistry, says their new agent killed cancer cells more quickly than cisplatin - a widely used chemotherapy drug that also kills cancer cells by attacking their DNA, but in a different way.
Prof. Glaser explains that much research on anticancer drugs has focused on variants of cisplatin, but the new copper complex is a completely new compound that they designed.
However, he also cautions that while the results in the lab show promise, their work is basic research:
"How and whether the copper complex will actually be given to cancer patients is something that medical research will have to determine in the years to come."
A potentially more effective alternative to cisplatin
Doctors have been using cisplatin as a chemotherapy agent for cancer for over 30 years. While the drug is effective against certain cancers - such as lung cancer and testicular cancer - it does not work for all cancers.
Also, cisplatin is not without side effects - it often causes nausea, vomiting and diarrhea. Another complication of cisplatin is that of drug resistance - a problem that often emerges with drugs that have been widely used for a long time.
For these reasons, Prof. Glaser and his lab wanted to find a completely new agent, unrelated to cisplatin, that would overcome these problems. The team focuses on making molecules not seen in nature and equipping them with specific tools.
The only similarity between the new copper molecule and cisplatin is that they both attack DNA of cancer cells, but how they do it is completely different.
DNA is a long-chain, complex molecule made of nucleobases, phosphates and sugar. Cisplatin works by attacking the nucleobases in cancer cell DNA, while the new copper molecule works by attacking the phosphates.
New copper molecule binds to phosphates on cancer cell DNA
The team designed the molecule to preferentially bind with the phosphates on the DNA - like a key that fits uniquely inside a lock. This binding interferes with how the DNA controls the working of the cancer cell so it cannot replicate itself, and it eventually dies.
The binding occurs in two places between the copper molecule and the DNA. The copper ions sit at two points protruding from the molecule - like a horseshoe presenting its two ends. The distance between the two points of the "horseshoe" is exactly the same as the distance between the phosphates in the DNA, so the molecule docks snugly onto the DNA.
"Because two phosphates bind simultaneously, the binding strength is greater. And that increases the efficacy," says Prof. Glaser.
In another part of the study, the team showed that the new compound has the potential to stop cancer cells reproducing themselves. When cells replicate, they produce copies of their DNA in a similar way to what happens in a polymerase chain reaction (PCR). In their study, the team confirms that the copper complex stops this reaction.
And finally, the team added the new molecule to a culture of cancer cells. Prof. Glaser says "the copper complex is more effective than cisplatin," and notes:
"The highest number of cancer cells died at a concentration of 10 micromolar. With cisplatin, you need 20 micromolar."
The team has also devised a way to manufacture the new copper complex.
In June 2014, Medical News Today learned how another copper compound may form the basis of the first therapy for ALS or Lou Gehrig's disease. The team that made the discovery believes that with further improvements and following the necessary trials to test the compound's safety and effectiveness in humans, it may also have potential to treat Parkinson's disease.