Specific stabilization of DNA triple helices by indolo[2,1-b]quinazolin-6,12-dione derivatives

Derivatives of indolo[2,1-b]quinazolinone containing aminoalkylamino side chains were synthesized as specific DNA triplex stabilizing agents. The aminoalkylamino side chains are essential for triplex stabilization. The position-8 fluorine atom or a methyl group to the nitrogen adjacent to the planar core can enhance triplex stability by 6 °C and the effect is additive. Conformational analysis reveals that the orientation of the side chain underlies the ability of this compound to stabilize a DNA triplex.

Slight structural modification with large triplex stabilizing effect. The position-8 F atom or a CH3 group to the nitrogen adjacent to the planar core enhances triplex stability and the effect is additive.Figure optionsDownload as PowerPoint slide