Interacción de ARN con doxorrubicina: Influencia del ligando y del metal en la actividad biológica de complejos organometálicos

Anticancer Activity of Half-Sandwich Ru, Rh and Ir Complexes with Chrysin Derived Ligands: Strong Effect of the Side Chain in the Ligand and Influence of the Metal

“…As expected, HL4 shows a different trend in SC migration with respect to its complexes, which reinforces the hypothesis that the metal center plays a key role in the interaction with DNA [129]. Since only the iridium complex display DNA chemical nuclease activity, the underlying mechanism was further investigated by means of a cleavage electrophoresis assay in which several well-known radical scavengers such as DMSO for OH • , L-histidine for 1 O2, sodium pyruvate for H2O2 and superoxide dismutase (SOD) for O2 − were included (Figure 9) [129]. Treatment of pUC18 with a high concentration of L4-Ir (lane 14) causes the vanishing of the SC form and an increase in the amount of the OC and L topologies.…”

“…The highest DNA contour length enhancement was observed for the HL4/DNA system. These data confirm the influence of both the ligand and the metal center on the intercalation process [129].…”

“…In addition to differences in biological behavior, such as the generation of ROS, the differences in the cytotoxicity amongst different compounds may also be related to their success in getting into cells. Hence, inductively coupled plasma mass spectrometry (ICP-MS) was employed to quantify the amount of metal inside A549 cells treated with the L4complexes during 24 h (Figure 13) [129]. The accumulation of all the complexes was higher than that determined for cisplatin.…”

“…The proligand HL4 also induced a decrease in molar ellipticity of the DNA intrinsic CD bands and the appearance of a small ICD band (Figure 6D). These features in DNA titrations with HL4 and L4-M complexes are related to the unwinding of the DNA double helix as a consequence of the drug intercalation between the DNA base pairs [129].…”

“…The ability of L4-Ir to generate singlet oxygen constitutes an important advantage for its potential as antitumor agent over its analogues, since singlet oxygen is identified as one of the major ROS produced in mitochondria and altering its levels is reported as an efficient strategy for cancer therapy [131]. Since only the iridium complex display DNA chemical nuclease activity, the underlying mechanism was further investigated by means of a cleavage electrophoresis assay in which several well-known radical scavengers such as DMSO for OH • , L-histidine for 1 O 2 , sodium pyruvate for H 2 O 2 and superoxide dismutase (SOD) for O 2 were included (Figure 9) [129]. Treatment of pUC18 with a high concentration of L4-Ir (lane 14) causes the vanishing of the SC form and an increase in the amount of the OC and L topologies.…”