DNA binding studies of a series of potential anti-tumor agents: Thiosemicarbazone ligands and their palladium (II) metal complexes.

摘要

DNA is the primary pharmacological target of many antitumor drugs, as well as antiviral and antibacterial agents. Depending on the mode of interaction of the complexes with DNA, the complexes can distort the double helical structure of DNA, alkylate or cleave a DNA strand thereby inhibiting DNA replication and transcription which are the necessary preconditions for cell division. Based on the current literature, the phenanthrenequinone thiosemicarbazone (PQ-TSC) and quinoline-2-carboxyaldehyde (QCA-TSC) complexes are potential antitumor agents. Therefore, DNA binding studies of PQ-TSC and QCA-TSC and their respective palladium metal complexes could shed light on the mechanism of DNA interaction which is important for understanding and designing new and more effective drugs with fewer side effects. To study the interaction of the complexes with calf thymus DNA, two spectroscopic techniques, namely absorption titration and competitive ethidium bromide fluorescence assay, were performed. Analysis of the results by absorption titration indicated that all twelve compounds examined showed hypochromicity and interacted with calf thymus DNA. The binding constant values of the complexes were calculated with calf thymus DNA. The lower binding constant obtained for the PQ-BzTSC could be due to the steric constraints exhibited by the benzyl group when the compound interacts with DNA. The binding constant values calculated for QCA metal complexes were higher than the corresponding ligands which could be attributed to the greater planar area exhibited by the metal complexes than the ligands. Fluorescence spectroscopic titrations with ethidium bromide were performed to calculate the linear Stern Volmer quenching constant and to differentiate between the different binding modes of DNA interaction. The results observed indicate that the PQ and QCA series bind with a partial, nonclassical intercalation mode