Phosphorus compounds made by scientists in India and the US have shown anticancer activity without using metals.
"The activities of the new compounds are comparable to known anticancer agents, such as cisplatin"
Maravanji Balakrishna and Dulal Panda's team at the Indian Institute of Technology, Mumbai, and Tulane University, New Orleans, US, has created metal-free compounds with a view to developing novel cancer therapies. Metal-based drugs such as platinum-based cisplatin have been used in cancer treatment for many years. But these compounds often induce unwanted side-effects, such as metal-based toxicity, which has encouraged the search for non-metal cancer drugs.
'And current metal-free anticancer drugs like taxanes involve multi-step synthesis with a relatively low yield,' says Balakrishna. His team's new compounds have the advantage of being simple to make and develop.
Phosphite chalcogen compounds show anticancer activity
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The team's compounds are based on phosphites - previously unexplored as anticancer agents - which showed promising effects when tested on human cancer cell lines. The team was particularly interested in one chalcogen derivative - finding that adding sulfur to a phosphite increased its effectiveness. They found that this compound not only activated p53, a tumour suppressor protein, in cells with a functional version of the protein but that it also caused cell death in cells with non-functional protein.
'It is significant if a drug can induce apoptosis in both the cell lines that have functional and non-functional p53, since p53 is lost or non-functional in most cancer cells,' explains Balakrishna. 'Many anticancer drugs also induce apoptosis both in a p53 dependent as well as an independent manner; the activities of our compounds are comparable to known anticancer agents, such as cisplatin.'
The next step for the team will be to develop the compounds further: 'This is the first step towards less toxic, water-soluble phosphorus compounds that prevent cell proliferation,' says Balakrishna.
Jon Silversides