title: The influence of positional isomerism on G-quadruplex binding and anti-proliferative activity of tetra-substituted naphthalene diimide compounds.
abstract: The synthesis together with biophysical and biological evaluation of a series of tetra-substituted naphthalene diimide (ND) compounds, are presented. These compounds are positional isomers of a recently-described series of quadruplex-binding ND derivatives, in which the two N-methyl-piperidine-alkyl side-chains have now been interchanged with the positions of side-chains bearing a range of end-groups. Molecular dynamics simulations of a pair of positional isomers are in accord with the quadruplex stabilization and biological data for these compounds. Analysis of structure-activity data indicates that for compounds where the side-chains are not of equivalent length then the positional isomers described here tend to have improved cell proliferation potency and in some instances, superior quadruplex stabilization ability.
authors.affiliation: The School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK.
authors.forename: Sheila
authors.initials: S
authors.lastname: Mpima
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Ohnmacht
authors.forename: Maria
authors.initials: M
authors.lastname: Barletta
authors.forename: Jarmila
authors.initials: J
authors.lastname: Husby
authors.forename: Luke C
authors.initials: LC
authors.lastname: Pett
authors.forename: Mekala
authors.initials: M
authors.lastname: Gunaratnam
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Hilton
authors.forename: Stephen
authors.initials: S
authors.lastname: Neidle
mesh_terms: D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D054856:G-Quadruplexes; D006801:Humans; D007094:Imides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D007536:Isomerism; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D009281:Naphthalenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D007094:Imides; D009281:Naphthalenes; C542131:naphthalenediimide
keywords: G-quadruplex; Molecular dynamics; Naphthalene diimide; Pancreatic cancer