Ruthenium(II) Complexes Coupled by Erianin Via a Flexible Carbon Chain as a Potential Stabilizer of c-myc G-Quadruplex DNA

Abstract

Herein, two novel ruthenium(II) complexes coupled by erianin via a flexible carbon chain, [Ru(phen)2(L1-(CH2)4-erianin)](ClO4)2 (L1 = 2-(2-(tri-fluoromethyphenyl))-imidazo [4,5f][1-10]phenanthroline (1) and [Ru(phen)2(L2-(CH2)4-eria)](ClO4)2 (L2 = 2-(4-(tri-fluoromethyphenyl))-imidazo [4,5f][1,10]phenanthroline (2), have been synthesized and investigated as a potential G-quadruplex(G4) DNA stabilizer. Both complexes, especially 2, can bind to c-myc G4 DNA with high affinity by electronic spectra, and the binding constant calculated for 1 and 2 is about 15.1 and 2.05 × 107 M-1, respectively. This was further confirmed by the increase in fluorescence intensity for both complexes. Moreover, the positive band at 265 nm in the CD spectra of c-myc G4 DNA decreased treated with 2, indicating that 2 may bind to c-myc G4 DNA through extern groove binding mode. Furthermore, fluorescence resonance energy transfer (FRET) assay indicated that the melting point of c-myc G4 DNA treated with 1 and 2 increased 15.5 and 16.5 °C, respectively. Finally, molecular docking showed that 1 can bind to c-myc G4 DNA in the extern groove formed by base pairs G7-G9 and G22-A24, and 2 inserts into the small groove of c-myc G4 DNA formed by base pairs T19-A24. In summary, these ruthenium(II) complexes, especially 2, can be developed as potential c-myc G4 DNA stabilizers and will be exploited as potential anticancer agents in the future.