Metal-DNA adducts are popular molecules for cancer treatment. However, the metal-based drugs have been associated with unwanted side effects such as nausea, nephrotoxicity (toxicity to kidney cells), and myelosuppression (suppression of bone marrow activity). Researchers have therefore been geared toward synthesizing metal-free cancer drugs. A research team at the Indian Institute of Technology in Bombay has created a new bis(phosphite) ligand) and corresponding complexes of selenium and gold with thioether functionalities (D. Suresh, Maravanji S. Balakrishna, Krishnan Rathinasamy, Dulal Panda and Joel T. Mague Dalton Trans., 2008, 2285 – 2292).
All three compounds were examined for cytotoxic activity in a HeLa (human cervix epitheloid carcinoma) cell line. While the bis(phosphite) ligand and bis(sulfide) derivative of the ligand significantly inhibited growth of the HeLa cells, the selenium and gold complexes did not. By testing both the bis(phosphite) ligand and bis(sulfide) derivative in the HeLa line with annexin V and a propidium iodide apoptosis detection kit, the researchers discovered that both compounds caused cell death by apoptosis, using specialized mechanisms within the cell to shed membrane-bound particles. The creation of a cancer drug that could potentially reduce or eliminate the side effects of metal-based drugs could help make treatment more bearable for patients as well as possibly attack resistant cells more effectively.