Novel naphthalimide hydroperoxide photonucleases: the role of thiocyclic-fused area and the difference in spectra, photochemistry and photobiological activity

Bioorg Med Chem. 2003 Dec 1;11(24):5427-33. doi: 10.1016/j.bmc.2003.09.026.

Abstract

Novel five- and six-membered thiocyclic-fused naphthalimide hydroperoxides (7, 8) as photonucleases were designed, synthesized via unusual isomerization in Pschorr cyclization and photooxygenation. The five-membered 7 was able to induce single-strand nicks in duplex DNA pH independently (7.0-8.5) at 0.5 microM under 366 nm, while the six-membered 8 could photonick the duplex DNA pH dependently (7.0-8.5) at 5 microM under 450 nm and showed 'time-controlled' photo-bioactivity. Their thiocycles and the angular conjugated plane have contributions to their binding affinity with DNA and photocleaving efficiency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclization
  • DNA / drug effects
  • DNA / radiation effects
  • DNA, Superhelical / drug effects
  • Deoxyribonucleases / chemistry*
  • Deoxyribonucleases / metabolism
  • Hydrogen-Ion Concentration
  • Imides / chemical synthesis
  • Imides / pharmacology*
  • Molecular Structure
  • Naphthalenes / chemical synthesis
  • Naphthalenes / pharmacology*
  • Peroxides / chemical synthesis
  • Peroxides / pharmacology*
  • Photochemistry
  • Spectrophotometry, Ultraviolet
  • Sulfhydryl Compounds / pharmacology*

Substances

  • DNA, Superhelical
  • Imides
  • Naphthalenes
  • Peroxides
  • Sulfhydryl Compounds
  • DNA
  • Deoxyribonucleases