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Abstract

Novel homodinuclear Cu(II) (K1), heterodinuclear Cu(II)-Mn(II) (K2) and homotrinuclear Cu(II) (K3) complexes with a novel oxime-type ligand have been prepared and their nucleolytic activities on pCYTEXP were established by neutral agarose gel electrophoresis. The analyses of the cleavage products obtained electrophoretically indicate that although the examined complexes induces very similar conformational changes on supercoiled DNA by converting supercoiled form to nicked form than linear form in a sequential manner as the complex concentration or reaction period is increased, K3 is less effective than the two others. The oxime complexes were nucleolytically active at physiological pH values but the activities of Kl or K2 were diminished by increasing the pH of the reaction mixture. In contrast, K3 makes dominantly single strand nicking by producing nicked circles on DNA at almost all the applied pH values. Metal complex induced DNA cleavage was also tested for inhibition by various radical scavengers as superoxide dismutase (SOD), azide, thiourea and potassium iodide. The antioxidants inhibited the nucleolytic acitivities of the oxime complexes but SOD afforded no protection indicating that the nucleolytic mechanism involves of copper and/or manganese complex-mediated reactive oxygen species such as hydroxyl radicals being responsible for the oxidative DNA cleavage.

Oxidative DNA cleavage by Schiff base tetraazamacrocyclic oxamido nickel(II) complexes

“…It has been proven that some reactive oxygen species, such as hydroxyl radicals, may be produced during the reactions of metal complexes with DNA, and these reactive oxygen species may be responsible for the oxidative DNA cleavage. It is well known that high pH conditions may be favorable for the formation of such reactive oxygen species [25,26]. …”

A DFT study of a novel oxime anticancer trans platinum complex: Monofunctional and bifunctional binding to purine bases

“…The cytotoxicity of the novel complex was examined in NRK-52E rat renal tubular cells and HepG2 human hepatoma cells, and the results indicated that the trans-platinum complex caused death by apoptosis, making the complex potentially suitable for therapeutic purposes. Furthermore, oxime molecules were selected as new ligands, not only because water solubility could be augmented for the platinum derivatives, but also because of their biological effects, such as endothelium independent relaxation in blood vessels [24], oxidative DNA cleavage [25], an increase in the targeting of specific nuclear bases of DNA [26], and a change in the antitumor action [27]. Additionally, some trans-Pt complexes with isopropylamine ligand have been studied that they exhibited higher activity in tumor cell lines which are sensitive and resistant to cisplatin [28][29][30].…”

Synthesis, crystal structure, DNA interaction and antioxidant activities of two novel water-soluble Cu(2+) complexes derivated from 2-oxo-quinoline-3-carbaldehyde Schiff-bases

“…Generally, the transition metals play a very important role in organism and their complexes can interact non-covalently with nucleic acid by intercalation, groove-binding or external electrostatic binding for cations [3,[7][8][9][10][11]. And that many transition metal complexes have been investigated to be utilized as probes of DNA structure, agents for mediation of strand scission of duplex DNA and chemotherapeutic agents [12][13][14]. Most notably, some Pt(2þ) complexes (cisplatin and carboplatin) have found their way into the pharmaceutical armamentarium as applied clinical antitumor drugs [15].…”