European consortium creates series of molecules could revolutionise chemotherapy drugs
Life
Alex Gibney and Prof Andrew Kellett, DCU
Scientists at Dublin City University (DCU, Ireland), in collaboration with research teams in Chimie ParisTech – PSL (France), Chalmers University of Technology, Sahlgrenska University Hospital, Gothenburg (Sweden), and the University of Limerick (Ireland), have developed a new chemical strategy for designing metal-based compounds capable of damaging cancer cell DNA, offering a potential new direction for future anticancer drug development.
Led by Prof Andrew Kellett, the European consortium has created a series of molecules that cut DNA through a distinct chemical mechanism compared with existing chemotherapy drugs. The research focuses on early-stage compounds that could form the basis of future therapies, particularly in cancers that become resistant to treatment.
The scientists used click chemistry – a fast and reliable method for assembling molecular components – to create a family of compounds known as tri-click ligands. When combined with copper ions, these ligands form artificial metallo-nucleases, metal-containing agents designed to cleave DNA.
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. A key advantage of this new chemical strategy is that the compounds damage DNA via pathways that differ from those targeted by many current cancer treatments. This means they may avoid some of the typical mechanisms that cancers use to become resistant.
Prof Kellett explained: “Click chemistry has transformed how we build complex molecules, but its potential as a platform to assemble DNA-damaging chemotherapeutics is under-explored. 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.”
Prof Damien Thompson, Director of SSPC, the Research Ireland Centre for Pharmaceuticals and professor of molecular modelling at UL, said: “This work exemplifies the value of systematic, deep screening of molecular properties in the development of more effective medicines. 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.”
Prof Gilles Gasser, professor of Bioinorganic Chemistry at Chimie ParisTech, said: “This work is clear evidence of the potential of metal-based compounds for anticancer research, going beyond the currently heavily used platinum-based drugs. While still in its infancy, this study is a first step towards new solutions for cancer treatment.”
TechCentral Reporters