Chromone‐Appended Zn(II) tRNA‐Targeted Potential Anticancer Chemotherapeutic Agent: Structural Details, in vitro ct‐DNA/tRNA Binding, Cytotoxicity Studies And Antioxidant Activity

Abstract

A 3-formyl-chromone-appended zinc(II) intercalator drug candidate of the formulation [bis(chromone)(H 2 O) 2 Zn(II)] was prepared as a potent anticancer agent and thoroughly characterized by multi-spectroscopic and single X-ray crystallographic studies. Preliminary binding studies of complex 1 with ct-DNA/tRNA were carried out employing various complementary biophysical techniques and the corroborative results of these experiments suggested strong binding propensity via intercalation binding mode towards ct-DNA/tRNA therapeutic targets, with higher preference for tRNA as quantified by binding constant { K b , K and K sv } parameters. The cleavage studies with pBR322 DNA were performed which implied that 1 cleaved the DNA by hydrolytic cleavage pathway which was further validated by T4 religation assay. Moreover, 1 was found to exhibit the tRNA cleavage behavior in a concentration and time-dependent manner. The cytotoxicity of complex 1 was evaluated against Huh-7, DU-145 and the PNT2 cell lines by MTT assay. A dose-dependent growth inhibition of the Huh-7 and DU-145 cells at low micromolar concentrations was observed and in another set of experiments, lipid peroxidation & glutathione (GSH) depletion were induced in the presence of the tested drug candidate. Interestingly, drug candidate 1 demonstrated selective cytotoxic activity for the DU-145 cancer cell line with LC 50 value of 3.2 μM which was further visualized by confocal microscopy.

Synthesis, structural insights, and biological screening of DNA targeted Ru(ii)(η6-p-cymene) complexes containing bioactive amino-benzothiazole ligand scaffolds

“…The CD spectral shifts support the interaction of complexes with ct-DNA which caused a modest disturbance of the secondary structure of ct-DNA. 41…”

“…The CD spectral shifts support the interaction of complexes with ct-DNA which caused a modest disturbance of the secondary structure of ct-DNA. 41 Cyclic voltammetry gives comprehensive and significant information about the redox behaviour of a complex and is regarded as a representative in vitro approach for elucidating the redox nature of a molecule in body fluids. 42 The change in the redox behaviour of a molecule measured in terms of the change in potential or current provides a way to probe their binding interactions with target molecules, which could aid in the investigations of a molecule as a potential drug candidate.…”

Antimicrobial and Bioinformatic Modelling Studies of Isatin Mixed Ligand and Some Ternary Chelates

“…The need to synthesize and develop new antibiotics is a principal demand. Targeting this goal, the synthesized compounds have been evaluated using MOE 2008 software to study molecular docking to assure their efficient interaction and their binding energy with the examined proteins [68,69] …”

“…Targeting this goal, the synthesized compounds have been evaluated using MOE 2008 software to study molecular docking to assure their efficient interaction and their binding energy with the examined proteins. [68,69] From the data presented, we have noticed that Cu(II) complex has the highest interaction with the receptors of crystal structure of S. aureus nucleoside (PDB ID: 3Q8U) with minimum binding energy of À 2 l.5 kcal/mol, Figure 4g. However, [Ni(ISA)(TMEDA)Cl 2 ] complex shows higher interaction than the free ligand with minimum binding energy À 7.2 kcal/ mol of the receptors of crystal structure of E. coli (PDB: 3T88), Figure 5f.…”