The (4S -FPro and (4S -FPro derivandves were compared to peptides containing 3,4R -FProoproline (Dh-Pro, 6) (Benedetti et al. 1981; Fisher et al. 1978), and the α-methylproline (αMe-Pro, 7) (Welsh et al. 1992; Hinds et al. 1991) with respect to binding and intercalation in dsDNA (Fig. 2).
Modeling revealed that the simultaneous covalent binding at G12 and intercalation of Dox between the A10 T16 and C11 G15 occurred with minimal distortion to the structure of the hairpin loop.
All the obtained compounds have been tested for their in vitro cytotoxic activity and the most potent of them showed an IC50 of 9 μM upon the human lung cancer (A-549) cell and a binding constant, for the intercalation with calf thymus DNA, of 9.6 × 104 M−104
In addition to this protein binding and CT-DNA intercalation studies showed molecules are highly potential.
The data indicate that both ligands interact with CT-DNA via a combined mode of action involving both groove binding and non-classical intercalation, while in the case of the complexes covalent bond formation takes place as well.
Figure 7 TEM images of the nanocomposite before and after intercalation with levodopa.
Furthermore, several maltol-derived compounds have been synthesised and exploited in the formulation of new potential metal-based antitumour drugs that can interfere with DNA (e.g., DNA binding, DNA intercalation and ROS generation), providing interesting results (Jakupec and Keppler, 2004; Barve et al, 2009; Kandioller et al, 2009).
Association and intercalation of AMPKα2 with myofibrils was evident in α-actinin co-stained cardiomyocytes (Fig. 3D right).
Biophysical studies showed that DNA dyes bind to dsDNA by intercalation and external binding, and that these interactions could interfere with PCR [ 2- 4].
Growth inhibition of HT29 cells by C1311 was concomitant with rapid drug accumulation in nuclei and in this context we showed that the compound binds to duplex DNA by intercalation, with likely A/T sequence-preferential binding.
