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Naproxen intercalates with DNA and causes photocleavage through ROS generation
Author(s) -
Husain Mohammed A.,
Yaseen Zahid,
Rehman Sayeed U.,
Sarwar Tarique,
Tabish Mohammad
Publication year - 2013
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12558
Subject(s) - naproxen , ethidium bromide , chemistry , dna , intercalation (chemistry) , agarose gel electrophoresis , flurbiprofen , biophysics , photochemistry , biochemistry , organic chemistry , pharmacology , alternative medicine , pathology , biology , medicine
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 .