A team of chemists at Bielefeld University in Germany says they have developed a molecule containing copper that binds specifically with DNA and prevents the spread of cancer. First results show that it kills the cancer cells more quickly than cisplatin, which is a widely used anticancer drug that is frequently administered in chemotherapy.
According to Thorsten Glaser, Ph.D., “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.
Since the end of the 1970s, doctors have been using cisplatin to treat cancer. For lung cancer and testicular cancer, the drug promotes healing; however, it does not work for all types of cancer. Cisplatin is also one of the anticancer drugs that most frequently induce nausea, vomiting, and diarrhea. “Therefore we wanted to develop an alternative agent that would work differently, have fewer side effects, and treat other types of cancer as well,” notes Dr. Glaser, professor of inorganic chemistry at Bielefeld University. “In addition, we wanted an agent that would treat cancers that have become immune to cisplatin through its use in earlier treatments.”
He and his colleagues are using methods from chemistry to produce new molecules that are not found in nature, and to equip these with specific properties.
Cisplatin attacks the DNA of cancer cells. While cisplatin binds with the nucleotides, the new molecule focuses on DNA’s phosphate backbone. The chemists did this by integrating two metal ions of copper in the molecule that preferentially bind with phosphates. As soon as the ions bind with the phosphate, the DNA of the cancer cell changes. This disrupts the cellular processes, prevents the cell from reproducing, and leads to the destruction of the pathological cell.
“We successfully synthesized the [copper] complex of the designed family of dinuclear complexes and studied its binding to dsDNA by independent ensemble and single-molecule methods like gel electrophoresis, precipitation, and titration experiments followed by UV vis spectroscopy, atomic force microscopy, as well as optical tweezers, and magnetic tweezers DNA stretching,” wrote the investigators in their study (“Rational Design of a Cytotoxic Dinuclear Cu2 Complex That Binds by Molecular Recognition at Two Neighboring Phosphates of the DNA Backbone”), which appears in Inorganic Chemistry. “The observed irreversible binding of our dinuclear [copper] complex to dsDNA leads to a blocking of DNA synthesis as studied by polymerase chain reactions and cytotoxicity for human cancer cells.”
The scientists applied the copper complex to cancer cells in cell culture. The result was that “the copper complex is more effective than cisplatin,” points out Dr. Glaser. “The highest number of cancer cells died at a concentration of 10 micromolar. With cisplatin, you need 20 micromolar.”
The development of new classes of anticancer drugs requires establishing other modalities for novel molecules to bind to nucleotides, concluded the scientists.