Synthesis of phenanthridine spiropyrans and studies of their effects on G-quadruplex DNA

Org Biomol Chem. 2017 Apr 11;15(15):3265-3275. doi: 10.1039/c7ob00300e.

Abstract

G-quadruplex (G4) DNA structures are involved in many important biological processes and can be linked to several human diseases. Drug-like low molecular weight compounds that target G4 structures are therefore interesting not only for their potential therapeutic properties but also for their potential use as chemical research tools. We report here on the development of methods to synthesize spiropyrans using a condensation-cyclisation reaction of quaternary salts of α-methyl quinoline or phenanthridine with salicylaldehydes. Evaluation of the synthesized phenanthridine spiropyrans' interactions with G4 DNA was performed with a Thioflavin T displacement assay, circular dichroism, Taq DNA polymerase stop assay, and NMR. This revealed that the substitution pattern on the phenanthridine spiropyrans was very important for their ability to bind and stabilize G4 structures. Some of the synthesized low molecular weight spirocyclic compounds efficiently stabilized G4 structures without inducing structural changes by binding the first G-tetrad in the G4 structure.

MeSH terms

  • Benzopyrans / chemical synthesis*
  • Benzopyrans / chemistry
  • Benzopyrans / pharmacology*
  • Chemistry Techniques, Synthetic
  • DNA / chemistry*
  • DNA / genetics
  • G-Quadruplexes / drug effects*
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Molecular Weight
  • Nitro Compounds / chemical synthesis*
  • Nitro Compounds / chemistry
  • Nitro Compounds / pharmacology*
  • Phenanthridines / chemistry*

Substances

  • Benzopyrans
  • Indoles
  • Nitro Compounds
  • Phenanthridines
  • spiropyran
  • DNA