1. Academic Validation
  2. The influence of positional isomerism on G-quadruplex binding and anti-proliferative activity of tetra-substituted naphthalene diimide compounds

The influence of positional isomerism on G-quadruplex binding and anti-proliferative activity of tetra-substituted naphthalene diimide compounds

  • Bioorg Med Chem. 2013 Oct 15;21(20):6162-70. doi: 10.1016/j.bmc.2013.05.027.
Sheila Mpima 1 Stephan A Ohnmacht Maria Barletta Jarmila Husby Luke C Pett Mekala Gunaratnam Stephen T Hilton Stephen Neidle
Affiliations

Affiliation

  • 1 The School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK.
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.

Keywords

G-quadruplex; Molecular dynamics; Naphthalene diimide; Pancreatic cancer.

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