Magnetic nanotemplate for developing anticancer drugs
doi:10.1038/nindia.2019.5 Published online 20 January 2019
Researchers have synthesised a magnetic nanotemplate that can pull out potential drug molecules from a mixture of small organic compounds1. Since the nanotemplate contains a specific DNA target that has a role in cancer, it could be used to identify molecules with anticancer potential — a technique that may help design novel anticancer drugs.
Current drug-design techniques such as dynamic combinatorial chemistry employ a template that identifies potent drug molecules from a mixture of small molecules. These techniques, however, have mostly come up with potential drug molecules that are unstable inside the cells.
To identify better drug candidates, scientists from the Indian Association for the Cultivation of Science in Kolkata, India, prepared the magnetic nanotemplate by coating magnetic nanoparticles with gold and attaching G-quadruplex DNA, a specific DNA structure that regulates the expression of cancer-causing genes. This DNA structure acts as a potential drug target.
The researchers, led by Jyotirmoyee Dash, then added the nanotemplate to a mixture of aldehyde- and amine-based building blocks. They found that three potent lead molecules bound strongly to the template.
Using an external magnet, they separated the lead molecules from the template and tested their anticancer properties by incubating them with human cervical and lung cancer cells. Of these three molecules, one proved to be most potent in repressing the activity of c-MYC genes, which play vital roles in tumour growth and progression.
Dash says that they next aim to develop potential drugs candidates for other DNA, RNA and protein targets, using a diverse and large library of building blocks.
1. Jana, S. et al. Dynamic generation of G‑Quadruplex DNA ligands by target-guided combinatorial chemistry on a magnetic nanoplatform. J. Med. Chem. (2018) doi: 10.1021/acs.jmedchem.8b01459