Influence of DMβCD on the Interaction of Copper(II) Complex of 6-Hydroxychromone-3-carbaldehyde-3-hydroxybenzoylhydrazine with ctDNA

Abstract

The interaction mechanism between a scarcely soluble copper­(II) complex of Cu­(II)-6-hydroxychromone-3-carbaldehyde-(3′-hydroxy)­benzoylhydrazone (CuCHz) in aqueous solution and its DMβCD complex was studied in the presence of ctDNA through spectroscopy and thermodynamic methods. The thermodynamic results indicate that the binding process of the CuCHz–DMβCD inclusion complex is a spontaneous process and the inclusion is enthalpy-driven. The binding constants of CuCHz and CuCHz–DMβCD with ctDNA are 2.69 × 103 and 14.7 × 103 L mol–1, respectively. The stoichiometry of the complex is 1:1, and the determined thermodynamic indicates that the process of binding is spontaneous and entropy-driven. A competitive binding titration with ethidium bromide revealed that CuCHz efficiently displaces EB from the EB–DNA system. In addition to the thermal denaturation experiments and docking studies, we can confirm that the mode of binding of this complex to ctDNA is intercalation mode. The presence of DMβCD enhances the aqueous solubility of CuCHz; nevertheless, the cyclodextrin did not affect the interaction of CuCHz with ctDNA because the inclusion complex breaks down when it binds with ctDNA.

Improvement in the Pharmacological Profile of Copper Biological Active Complexes by Their Incorporation into Organic or Inorganic Matrix

“…The system exhibits cell compatibility and a low cytotoxicity, and as a result can be studied as a bacc delivery material with controlled release [ 109 ]. The soluble complex [Cu(chz)Cl] (Hchzis 6-hydroxychromone-3-carbaldehyde-(3′-hydroxy)benzoylhydrazone) was spontaneously included in heptakis-2,6- O -dimethyl-β-cyclodextrin (DMβCD) and the inclusion complex was proven to bind CT DNA in an intercalative mode [ 110 ].…”

Facile synthesis of novel NNO-tethered copper(ii) complexes: characterization details, theoretical studies, promising enzyme-like activities, and biomolecular interactions

“…45–49 The complexes can covalently or non-covalently interact with DNA, a key target in cancer therapy, or they can trigger DNA hydrolysis or oxidative cleavage. 50–53 As a result, they interfere with DNA replication to ensure the death of the most rapidly proliferating cells.…”

Terpyridine copper(ii) complexes as potential anticancer agents by inhibiting cell proliferation, blocking the cell cycle and inducing apoptosis in BEL-7402 cells

“…11 Biocompatible copper complexes have attracted great attention due to their high affinity for nucleobases and their ability to disrupt the mitochondrial function and further cause tumor cell death via mechanisms different from those of platinum drugs. [12][13][14][15][16] Copper is present endogenously and copper complexes may be less toxic to normal cells. 17,18 Cu(II) complexes have several advantages including diverse oxidation states, good biocompatibility, and little side effects, to be developed as potential chemotherapeutic agents.…”