Evaluation of Acridine Orange Derivatives as DNA-Targeted Radiopharmaceuticals for Auger Therapy: Influence of the Radionuclide and Distance to DNA.

ABSTRACT: A new family of ^99mTc(I)- tricarbonyl complexes and ¹²⁵I-heteroaromatic compounds bearing an acridine orange (AO) DNA targeting unit was evaluated for Auger therapy. Characterization of the DNA interaction, performed with the non-radioactive Re and ¹²⁷I congeners, confirmed that all compounds act as DNA intercalators. Both classes of compounds induce double strand breaks (DSB) in plasmid DNA but the extent of DNA damage is strongly dependent on the linker between the Auger emitter (^99mTc or ¹²⁵I) and the AO moiety. The in vitro evaluation was complemented with molecular docking studies and Monte Carlo simulations of the energy deposited at the nanometric scale, which corroborated the experimental data. Two of the tested compounds,

SUBMITTER: Pereira E 

PROVIDER: S-EPMC5304164 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature