Diacrylamides as selective G-quadruplex ligands in in vitro and in vivo assays

MedChemComm
2011.0

Abstract

The synthesis of previously unreported anthracene-9-monoacrylamides and anthracen-9,10 bisacrylamides and their potential as G-quadruplex ligands were discussed based on preliminary fluorometric, biological assay, and NMR data. We conducted preliminary optimisation of the conditions for these C–C coupling reactions and fully characterised 8 previously unreported compounds that have the potential to afford a route to a range of conjugate addition products for the development of a G-quadruplex-templated dynamic combinatorial library. The promotion of quadruplex DNA formation, as observed in solution by NMR, coupled with compelling fluorescence data and initial biological testing, suggests the class of G-quadruplex ligand based on 4h possesses an anticancer activity, which renders this family of compounds worthy of further investigation in terms of both duplex/quadruplex selectivity, bioavailability and expansion of the series to better understand any QSAR that may exist.

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