Optimization of anti-proliferative activity using a screening approachwith a series of bis-heterocyclic G-quadruplex ligands

Using a phenotypic screening and SAR optimization approach, a phenyl-bis-oxazole derivative has beenidentified with anti-proliferative activity, optimized with the use of a panel of cancer cell lines. The leadcompound was synthesized by means of a short and effective two-step synthesis using Pd-catalyzeddirect arylation. The compound stabilizes several quadruplex DNA sequences including a human telomericDNA and one from the promoter of the HSP90 gene, although the structure–activity relationships of theseries are not obviously related to the quadruplex binding.