Synthesis, characterization, DNA binding and cleaving properties of photochemically activated phenanthrene dihydrodioxin

Abstract

Abstract Dihydrodioxin compounds are formed upon visible light irradiation of a mixture of an ortho-quinone and a substituted alkene. The reverse photochemical reaction can result in the release of a highly reactive ortho-quinone that can induce oxidative DNA damage. A novel DNA binding and cleaving phenanthrene dihydrodioxin compound (1) was synthesized. The photochemical release of 9,10-phenanthrenequinone was studied under different light irradiation wavelengths. Interaction of 1 with DNA caused an increase in the viscosity of DNA as well as hypochromic effect and a bathochromic shift in the absorption of 1. These results indicated the intercalative mode of binding of 1 to DNA. Binding affinities of 1 to several DNA sequences were evaluated, and slightly preferential binding to AT-rich DNA oligomers was observed. Intercalation of 1 between CT-DNA base pairs induced a partial transition from B-form to Z-form of DNA. Significant stabilization of the DNA duplex was revealed by DNA optical melting experiments with 33 % GC 12-mer (∆Tm = 9 oC). ΦX174 photocleavage assay showed that 1 is capable of > 90 % single-strand DNA cleavage and ∼ 5 % of double-strand DNA breakage. Therefore, 1 further demonstrates the potential of masked orhto-quinones as efficient photoactivated DNA cleaving agents.