Finding ligands capable of stabilising G-quadruplex DNA structures has been a hot topic in medicinal chemistry for a number of years now, due to their potential as anti-cancer treatments. But despite intensive research G-quadruplex ligands are yet to appear on the drug market-due to various problems with toxicity and efficacy-requiring the investigation of new, effective compounds.
Adam Le Gresley and colleagues from Kingston University have therefore investigated 8 anthracene-9-monoacrylamides and anthracen-9,10-bisacrylamides, which fit the criteria that has been identified for successful G-quadruplex binding. They were surprised that neither the synthesis nor biological evaluation of their chosen diacrylamides had previously been reported, and so characterise them fully here. They found that one class of ligand tested possesses anti-cancer activity, based on promotion of quadruplex DNA formation observed in solution by NMR, coupled with ‘compelling’ fluorescence data and initial biological testing. The group are now undertaking further investigations to better understand the activity of the diacrylamides.
Read more about this new class of potential G-quadruplex ligands – the paper is currently free to access:
Diacrylamides as selective G-quadruplex ligands in in vitro and in vivo assays
Adam Le Gresley, Ammara Abdullah, Deepak Chawla, Pratchi Desai, Uttam Ghosh, Uma Gollapalli, Munazza Kiran, Shehri Lafon and Alex Sinclair
Med. Chem. Commun., 2011, Advance Article
DOI: 10.1039/C1MD00020A
