title: Optimization of anti-proliferative activity using a screening approach with a series of bis-heterocyclic G-quadruplex ligands.
abstract: Using a phenotypic screening and SAR optimization approach, a phenyl-bis-oxazole derivative has been identified with anti-proliferative activity, optimized with the use of a panel of cancer cell lines. The lead compound was synthesized by means of a short and effective two-step synthesis using Pd-catalyzed direct arylation. The compound stabilizes several quadruplex DNA sequences including a human telomeric DNA and one from the promoter of the HSP90 gene, although the structure-activity relationships of the series are not obviously related to the quadruplex binding.
authors: UCL School of Pharmacy, University College London, London, UK.
authors: Stephan A
authors: SA
authors: Ohnmacht
authors: Cristina
authors: C
authors: Ciancimino
authors: Giulia
authors: G
authors: Vignaroli
authors: Mekala
authors: M
authors: Gunaratnam
authors: Stephen
authors: S
authors: Neidle
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D054856:G-Quadruplexes; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D013329:Structure-Activity Relationship
chemical_list: D006571:Heterocyclic Compounds; D008024:Ligands
keywords: Anti-proliferative; Oxazoles; Phenotypic screening; Quadruplex; Telomerase