Organoruthenium (II) complexes featuring pyrazole‐linked thiosemicarbazone ligands: Synthesis, DNA/BSA interactions, molecular docking, and cytotoxicity studies

Abstract

A series of pyrazol-derived thiosemicarbazone ligands (L1-L4) were synthesized and reacted with [Ru(p-cymene)(μ-Cl)Cl] 2 to yield a series of "piano-stool"-type binuclear ruthenium (II)-arene-thiosemicarbazone complexes (C1-C8) of the general type [(Ru(η 6 -p-cym)L) 2 (μ-im/azpy)] Cl 1-2 (L = diphenylpyrazole thiosemicarbazone; cym = p-cymene; im = imidazole; azpy = 4,4 0 -azopyridine). The thiosemicarbazone ligands act as N and S donors binding to the Ru(II) center via the imine nitrogen and the thione sulfur atoms. The complexes were characterized by NMR, FTIR, UV-Vis spectroscopy, and ESI + mass spectrometry. The binding of the complexes to calf thymus deoxyribonucleic acid (CT-DNA) and bovine serum albumin (BSA) was evaluated, and it has been established that the binuclear complexes have good binding efficacies with DNA (K b = 10 4 -10 5 M À1 ) and BSA (K a = 10 5 -10 6 M À1 ). This is attributed to the arene moieties present in the ligands of the complexes that can have hydrophobic interactions with DNA/BSA. Ethidium bromide (EB) displacement studies and DNA viscosity measurements revealed intercalative interaction of the complexes with DNA. Static interaction of the complexes with BSA was revealed by fluorescence quenching studies. Molecular docking studies confirmed base stacking, H-bonding, and hydrophobic interactions with the biomolecules. In vitro antiproliferative studies of the complexes affirmed that the complexes are cytotoxic towards the HeLa (human cervical cancer) cell line with IC 50 values in range of 17.3-41.3 μM. K E Y W O R D S binuclear ruthenium (II) complexes, DNA/BSA binding interactions, HeLa human cervical carcinoma, pyrazole-derived thiosemicarbazone

Visible Light-Prompted Regioselective Synthesis of Novel 5-Aroyl/hetaroyl-2′,4-dimethyl-2,4′-bithiazoles as DNA- and BSA-Targeting Agents

“…The inherent fluorescence property exhibited by proteins due to the presence of aromatic amino acid residues mainly tryptophan (Trp), tyrosine (Tyr), and phenylalanine (Phe) makes fluorescence spectroscopy a valuable tool to investigate the protein−ligand interaction. 54 In order to identify the binding forces between ligand 7g and BSA protein, emission experiments were executed at three different temperatures of 298, 303, and 308 K. A strong peak at 342 nm was observed when the emission spectra of native BSA were recorded in the spectral range of 290−500 nm by setting the excitation wavelength at 280 nm, and then, the BSA solution was titrated with an increasing amount of ligand 7g (0−26 μM) (Figure 14a−c). A gradual decrease in the emission intensity of BSA at 342 nm was observed with increasing concentration of ligand 7g, which eventually quenched at higher ligand concentration, indicating the preferable binding interactions between ligand 7g and BSA protein.…”