title: DNA cleavage by Cu(II)-desferal: identification of C1'-hydroxylation as the initial event for DNA damage.
abstract: Desferal, a siderophore of microbial origin is the only drug currently used for clinical treatment of a genetic disorder, thalassemia. By using a combination of HPLC and 31P-NMR, it is demonstrated that the Cu complex of desferal cleaves DNA, the primary site of hydroxyl radical attack being the sugar C1' in the minor groove, which leads to production of 5-methylene furanone. While no C5'-oxidation was observed, a minor process involving C4'-attack accompanies the above cleavage path. The oxidative cleavage of DNA observed with CuDFO may have implications in the emerging applications of desferal as a drug delivery agent and an antimalarial.
authors.affiliation: Bioorganic Chemistry Unit, National Chemical Laboratory, Pune, India.
authors.forename: R R
authors.initials: RR
authors.lastname: Joshi
authors.forename: S M
authors.initials: SM
authors.lastname: Likhite
authors.forename: R K
authors.initials: RK
authors.lastname: Kumar
authors.forename: K N
authors.initials: KN
authors.lastname: Ganesh
mesh_terms: D000818:Animals; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D003300:Copper / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D004249:DNA Damage; D003676:Deferoxamine / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005663:Furans / Q000032:analysis; D006900:Hydroxylation; D009682:Magnetic Resonance Spectroscopy; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010084:Oxidation-Reduction
chemical_list: D005663:Furans; D009942:Organometallic Compounds; C086943:copper-desferal complex; C037354:protoanemonin; D003300:Copper; D004247:DNA; D003676:Deferoxamine