title: Synthesis, reactive oxygen species generation and copper-mediated nuclease activity profiles of 2-aryl-3-amino-1,4-naphthoquinones.
abstract: Here we report a series of 2-aryl-3-amino-1,4-naphthoquinones that generated reactive oxygen species (ROS) such as superoxide and hydrogen peroxide upon incubation in pH 7.4 under ambient aerobic conditions. ROS generation from these compounds was sensitive to structural modifications at the 3-amino position and a 2-aryl substituent promoted ROS generation. A number of these compounds were found to induce DNA damage in the presence of Cu(II) without any added reducing agent. Our data suggests that 2-aryl-3-amino-1,4-naphthoquinones' propensity to produce ROS correlated well with its DNA damage inducing ability. 2-Phenyl-3-pyrrolid-1-yl-1,4-naphthoquinone (22) was found to damage DNA at 1 μM suggesting that these compounds may have therapeutic relevance in targeting cancers which over-express Cu(II).
authors.affiliation: Department of Chemistry, Indian Institute of Science Education and Research Pune, Pune, Maharashtra, India.
authors.forename: Vinayak S
authors.initials: VS
authors.lastname: Khodade
authors.forename: Allimuthu T
authors.initials: AT
authors.lastname: Dharmaraja
authors.forename: Harinath
authors.initials: H
authors.lastname: Chakrapani
mesh_terms: D003300:Copper / Q000737:chemistry*; D004249:DNA Damage / Q000187:drug effects; D003851:Deoxyribonucleases / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D009285:Naphthoquinones / Q000138:chemical synthesis / Q000737:chemistry*; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D009285:Naphthoquinones; D017382:Reactive Oxygen Species; D003300:Copper; D003851:Deoxyribonucleases; C035342:1,4-naphthoquinone