In a laboratory, preclinical study recently published by the journal Organic & Biomolecular Chemistry, Virginia Commonwealth University Massey Cancer Center researchers combined structural features from anti-nausea drug thalidomide with common kitchen spice turmeric to create hybrid molecules that effectively kill multiple myeloma cells.
Thalidomide was first introduced in the 1950s as an anti-nausea medication to help control morning sickness, but was later taken off the shelves in 1962 because it was found to cause birth defects. In the late 1990's the drug was re-introduced as a stand-alone or combination treatment for multiple myeloma. Turmeric, an ancient spice grown in India and other tropical regions of Asia, has a long history of use in herbal remedies and has recently been studied as a means to prevent and treat cancer, arthritis and Alzheimer's disease. According to the American Cancer Society, laboratory studies have shown that curcumin, an active ingredient in turmeric, interferes with several important molecular pathways and inhibits the formation of cancer-causing enzymes in rodents.
"Although thalidomide disturbs the microenvironment of tumor cells in bone marrow, it disintegrates in the body. Curcumin, also active against cancers, is limited by its poor water solubility. But the combination of thalidomide and curcumin in the hybrid molecules enhances both the cytotoxicity and solubility," says the study's 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 can provide certain advantages. "Enhanced potency, reduced risk of developing drug resistance, improved pharmacokinetic properties, reduced cost and improved patient compliance are just a few of those advantages," says another of the study's researchers Steven Grant, M.D., Shirley Carter Olsson and Sture Gordon Olsson Chair in Oncology Research, associate director for translational research, program co-leader of Developmental Therapeutics and Cancer Cell Signaling research member at VCU Massey Cancer Center.
The hybrid molecules of turmeric and thalidomide created more than 15 compounds, each with a different effect. Scientists found that compounds 5 and 7 exhibited superior cell toxicity compared to curcumin alone or the combination of curcumin and thalidomide. Furthermore, 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," added Grant. "The results also strongly encourage further optimization of compounds 5 and 7 to develop more potent agents as treatment options for multiple myeloma."
Zhang and Grant collaborated on this study with Kai Liu from the Department of Medicinal Chemistry at the VCU School of Pharmacy; Jeremy Chojnacki, from the VCU Department of Medicinal Chemistry; Datong Zhang, from the School of Chemistry and Pharmaceutical Engineering at Shandong Polytechnic University in Jinan, Shandong; and Yuhong Du and Haian Fu, from the Department of Pharmacology and Emory Chemical Biology Discovery Center at Emory University in Atlanta, Georgia.
The full manuscript of this study is available at: http://pubs.rsc.org/en/content/articlepdf/2013/ob/c3ob40595h.
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About VCU Massey Cancer Center
VCU Massey Cancer Center is one of only 67 National Cancer Institute-designated institutions in the country that leads and shapes America's cancer research efforts. Working with all kinds of cancers, the Center conducts basic, translational and clinical cancer research, provides state-of-the-art treatments and clinical trials, and promotes cancer prevention and education. Since 1974, Massey has served as an internationally recognized center of excellence. It has one of the largest offerings of clinical trials in Virginia and serves patients in Richmond and in four satellite locations. Its 1,000 researchers, clinicians and staff members are dedicated to improving the quality of human life by developing and delivering effective means to prevent, control and ultimately to cure cancer. Visit Massey online at http://www.massey.vcu.edu or call 877-4-MASSEY for more information.
About VCU and the VCU Medical Center
Virginia Commonwealth University is a major, urban public research university with national and international rankings in sponsored research. Located in downtown Richmond, VCU enrolls more than 31,000 students in 222 degree and certificate programs in the arts, sciences and humanities. Sixty-six of the programs are unique in Virginia, many of them crossing the disciplines of VCU's 13 schools and one college. MCV Hospitals and the health sciences schools of Virginia Commonwealth University compose the VCU Medical Center, one of the nation's leading academic medical centers. For more, see http://www.vcu.edu.
Organic & Biomolecular Chemistry