The team says this new chemical strategy could avoid some of the typical mechanisms that cancers use to become resistant.
A consortium that includes scientists from Dublin City University (DCU) and the University of Limerick (UL) has developed a new chemical strategy for designing metal-based compounds capable of damaging cancer cell DNA.
The team includes researchers from Chimie ParisTech from France, and Chalmers University of Technology and the Sahlgrenska University Hospital from Sweden.
Led by DCU’s Prof Andrew Kellet, the European consortium has created a series of molecules that cut DNA through a distinct chemical mechanism when compared with existing chemotherapy drugs. Their research focuses on early-stage compounds that could form the basis of future therapies, particularly in cancers that become resistant to treatment.
To achieve their results, the scientists used “click chemistry” – a method used for assembling molecular components – to create a family of compounds known as “tri-click” ligands. When combined with copper ions, these ligands form artificial metal-containing agents designed to cleave DNA.
“Click chemistry has transformed how we build complex molecules, but its potential as a platform to assemble DNA-damaging chemotherapeutics is under-explored,” said Kellet.
“One of the major challenges in cancer treatment is drug resistance. By developing compounds that damage DNA in a different way, we aim to open up new possibilities for overcoming some of the limitations of existing therapies. While this research is still at an early stage, it provides a valuable platform for future drug development.”
Drug resistance remains one of the biggest challenges in cancer treatment. Tumours can adapt by repairing specific forms of DNA damage or by blocking the activity of conventional drugs. According to the team, this new chemical strategy could avoid some of the typical mechanisms that cancers use to become resistant. Their study has been published in the journal Nature.
“This work exemplifies the value of systematic, deep screening of molecular properties in the development of more effective medicines,” said Damien Thompson, the director of SSPC, the Research Ireland Centre for Pharmaceuticals and a professor of molecular modelling at UL.
“Support from SSPC, the Research Ireland Centre for Pharmaceuticals enabled strong collaboration between our experimental and modelling teams and this new design strategy marks a key milestone in developing sustainable, well-tolerated anticancer drugs.”
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