Structural features from anti-nausea drug thalidomide combined with kitchen spice turmeric can create hybrid molecules that effectively kill multiple myeloma cells, say researchers at Virginia Commonwealth University Massey Cancer Center, who carried out a preclinical study.
Due to previous laboratory studies, it is known that curcumin, an active ingredient in turmeric, interferes with several important molecular pathways and inhibits the formation of cancer-causing enzymes in rodents. However, it is limited because of its poor water solubility.
It is also known that thalidomide disturbs the microenvironment of tumour cells in bone marrow, but that it also disintegrates in the body.
"But the combination of thalidomide and curcumin in the hybrid molecules enhances both the cytotoxicity and solubility," said study lead researcher Shijun Zhang, assistant professor in the Department of Medicinal Chemistry at the VCU School of Pharmacy.
Compared to mixing multiple drugs, creating hybrid molecules has certain advantages, including enhanced potency, reduced risk of developing drug resistance, improved pharmacokinetic properties, reduced cost and improved patient compliance.
Multiple myeloma is a cancer of plasma cells where collections of abnormal plasma cells accumulate in the bone marrow and interfere with the production of normal blood cells. It is more common in men, and for unknown reasons is twice as common in African-Americans as it is in European-Americans.
Thalidomide, which was first introduced in the 1950s as an anti-nausea medication to help control morning sickness, was taken off the shelves in 1982 because it was found to cause birth defects. The drug was reintroduced as a stand-alone or combination treatment for multiple myeloma in the 1990s.
Turmeric is an ancient spice grown in India and other tropical regions of Asia and has a long history of use in herbal remedies. Recently, it has been studied as a means to treat arthritis and Alzheimer’s disease.
Scientists found that the hybrid molecules of turmeric and thalidomide created more than 15 compounds, each with a different effect. However, compounds 5 and 7 exhibited superior cell toxicity compared to curcumin alone or the combination of curcumin and thalidomide.
Most notably, the compounds were found to induce significant multiple myeloma cell death.
"Overall, the combination of the spice and the drug was significantly more potent than either individually, suggesting that this hybrid strategy in drug design could lead to novel compounds with improved biological activities," said study researcher Steven Grant.
"The results also strongly encourage further optimisation of compounds 5 and 7 to develop more potent agents as treatment options for multiple myeloma," added Grant.
The full details of the study are published in the journal Organic & Biomolecular Chemistry.
Image: Turmeric flower. Photo courtesy of Sankarshansen.
