title: Naproxen intercalates with DNA and causes photocleavage through ROS generation.
abstract: Naproxen is an important non-steroidal anti-inflammatory drug with many pharmacological and biological properties. In this study, we have attempted to ascertain the mode of action and the mechanism of binding of naproxen to DNA. We have also demonstrated that, upon irradiation with white light, naproxen generates reactive oxygen species, causing DNA cleavage. Generation of reactive oxygen species from photo-irradiated naproxen as determined spectrophotometrically was found to lead to nicking of plasmid DNA as analyzed by agarose gel electrophoresis. Without photo-irradiation, naproxen binds to DNA and forms drug-DNA complexes as revealed by spectroscopic techniques. Several experiments such as determination of the effect of urea, iodide-induced quenching and a competitive binding assay with ethidium bromide showed that naproxen binds to DNA primarily in an intercalative manner. These observations were further supported by CD analysis, viscosity measurements and molecular docking. Using DNA as a template, fluorescence resonance energy transfer between naproxen and ethidium bromide was also observed, further strengthening the evidence for intercalative binding of naproxen with DNA.
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, A.M. University, Aligarh, Uttar Pradesh, India.
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Husain
authors.forename: Zahid
authors.initials: Z
authors.lastname: Yaseen
authors.forename: Sayeed U
authors.initials: SU
authors.lastname: Rehman
authors.forename: Tarique
authors.initials: T
authors.lastname: Sarwar
authors.forename: Mohammad
authors.initials: M
authors.lastname: Tabish
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001667:Binding, Competitive; D002417:Cattle; D002942:Circular Dichroism; D004247:DNA / Q000378:metabolism*; D053837:DNA Cleavage / Q000528:radiation effects*; D004996:Ethidium / Q000378:metabolism; D005453:Fluorescence; D031541:Fluorescence Resonance Energy Transfer; D007364:Intercalating Agents / Q000494:pharmacology*; D008027:Light; D008958:Models, Molecular; D009288:Naproxen / Q000494:pharmacology*; D011193:Potassium Iodide / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007364:Intercalating Agents; D017382:Reactive Oxygen Species; D011193:Potassium Iodide; D009288:Naproxen; D004247:DNA; C427203:calf thymus DNA; D004996:Ethidium
keywords: DNA binding; ROS; docking; intercalation; naproxen