Mechanistic insights into a novel chromone-appended Cu(ii) anticancer drug entity: in vitro binding profile with DNA/RNA substrates and cytotoxic activity against MCF-7 and HepG2 cancer cells

Abstract

A new chromone-appended Cu(ii) drug entity () was designed and synthesized as a potential anticancer chemotherapeutic agent. The structural elucidation was carried out thoroughly by elemental analysis, FT-IR, EPR, ESI-MS and single crystal X-ray crystallography. Complex resulted from the in situ methoxylation reaction of the 3-formylchromone ligand and its subsequent complexation with the copper nitrate salt in a 2 : 1 ratio, respectively. crystallized in the monoclinic P21/c space group possessing the lattice parameters, a = 8.75 Å, b = 5.07 Å, c = 26.22 Å, α = γ = 90°, β = 96.3° per unit cell. Furthermore, in vitro interaction studies of with ct-DNA and tRNA were carried out which suggested more avid binding propensity towards the RNA target via intercalative mode, which was reflected from its Kb, K and Ksv values. The gel electrophoretic mobility assay was carried out on the pBR322 plasmid DNA substrate, to ascertain the cleaving ability and the mechanistic pathway in the presence of additives, and the results revealed the efficient cleaving ability of via the oxidative pathway. In vitro cell growth inhibition via the MTT assay was carried out to evaluate the cytotoxicity of complex and IC50 values were found to be in the range of 5-10 μg mL(-1) in HepG2 and MCF-7 cancer cell lines, which were found to be much lower than the IC50 values of previously reported similar Cu(ii) complexes. Additionally, in the presence of , reactive oxygen species (ROS) and thiobarbituric acid reactive substance (TBARS) levels in the tested cancer cell lines increased significantly, coupled with reduced glutathione (GSH) levels. Thus, our results suggested that ROS plays an important role in cell apoptosis induced by the Cu(ii) complex and validates its potential to act as a robust anticancer drug entity.

Heteroleptic Copper(I) Complexes of “Scorpionate” Bis-pyrazolyl Carboxylate Ligand with Auxiliary Phosphine as Potential Anticancer Agents: An Insight into Cytotoxic Mode

“…Since circular dichroism (CD) is a technique highly sensitive to changes in the conformation of the chiral structure of DNA5255, it can be used to study the subtle variations upon its interaction with small molecules56575859. The CD spectrum of CT-DNA exhibits a positive band at 275 nm (UV, λ max  = 260 nm) caused by base stacking between the compounds and DNA, and a negative band at 245 nm caused by helicity, which is characteristic of DNA in right-handed B form.…”

Bioactive mono/bis (carboxyamide) based Co (II), Ni (II) and Cu (II) complexes: Synthesis, Characterization, DNA binding and Anticancer Potentials

“…MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay was carried out as described previously . The L and complexes 1–3 (0 – 300 μM), in DMSO were added to the wells containing 1 × 10 4 cells per well in 200 μL of fresh culture medium after their seeding for 24 hr.…”

Synthesis of chiral R/S-pseudopeptide-based Cu(ii) & Zn(ii) complexes for use in targeted delivery for antitumor therapy: enantiomeric discrimination with CT-DNA and pBR322 DNA hydrolytic cleavage mechanism

“…In vitro DNA binding studies DNA binding experiments, including absorption spectral traces, emission spectroscopy and circular dichroism, conformed to the standard methods and practices previously adopted by our laboratory, 40,41 whereas DNA cleavage was performed by the standard protocol as described previously. 42 While measuring the absorption spectra, an equal amount of DNA was added to both the compound solutions and the reference solution to eliminate the absorbance of the CT-DNA itself, and tris-HCl buffer was subtracted through base line correction.…”