New gold(III) chlorophenyl terpyridine complex: Biomolecular interactions and anticancer activity against human oral squamous cell carcinoma

Abstract

In this work we synthesized new monofunctional gold(III) complex [Au(Cl‐Ph‐tpy)Cl]Cl2 (Cl‐Ph‐tpy = 4′‐[4‐chlorophenyl]‐2,2′:6′, 2″‐terpyridine). This complex was characterized by UV–Vis, NMR, IR, and ESI‐MS spectrometry. The kinetic study of the substitution reactions of the Au‐Cl‐Ph‐tpy complex with biomolecules showed that the rate constants depend on the nature of the entering nucleophile. Based on the calculated values of entropy (∆H≠ > 0) and enthalpy (∆S≠ < 0) the proposed substitution mechanism is associative. Additionally, the relative stability and thermodynamic properties of Au‐Cl‐Ph‐tpy complex were compared with the analogue Au‐tpy complex by the B3LYP/def2‐svp method. DNA/BSA binding studies showed that Au‐Cl‐Ph‐tpy complex interacts with CT DNA through the intercalation and moderately quenches the fluorescence of tryptophan residues in serum albumin (BSA). Molecular docking confirmed results obtained by spectroscopic experiments and suggested site I (subdomain IIA) for binding of Au complex to BSA. We demonstrated that the Au chlorophenyl terpyridine complex possessed significant in vitro cytotoxic activity against human oral squamous carcinoma cells (CAL‐27), induced apoptosis, inhibited proliferation of CAL‐27 cells, and induced cell cycle disturbance. Treatment of CAL‐27 cells with the Au complex enhanced expression of cyclin‐dependent kinase inhibitors p21 and p27, resulting in cell cycle arrest in the G1 phase, reduced the percentage of CAL‐27 cells in S phase and decreased expression of Ki‐67. Additionally, Au complex reduced expression of phosphorylated STAT3 and downstream regulated molecules associated with cancer stemness, NANOG, and Sox2 protein.

New dinuclear gold(III) complex with 1,5-naphthyridine as bridging ligand: synthesis, characterization, DNA/BSA binding studies, and anticancer activity

“…The band at 265 nm corresponds to the intra-ligand (π → π*) charge transfer, while the bands at 300/305 nm and 310/315 nm are described as ligand-to-metal charge transfer (LMCT). [23] While the dinuclear gold(III) complex is neutral, the dissociation of one chloride ligand results in the corresponding molecular ion [C 8 H 6 Au 2 Cl 5 N 2 ] + (m/z 700.8246), which could be detected by Cryospray-MS analysis. Its recorded isotope pattern also ts the simulation, supporting this assignation (ESI, Fig.…”

“…Furthermore, the decrease in uorescence intensity is caused by the displacement of EB from EB-DNA system. [23] The uorescence titration of EB-DNA with the increasing concentration of dinuclear gold(III) complex (1.35-13.9 µM) is shown in Fig. 2.…”

“…[22] Because of its strong structural similarity with human serum albumin (HSA), bovine serum albumin (BSA), one of the most prevalent proteins in plasma, is used to study the potential mechanism of binding of metal complexes to proteins. [23] Considering the previously mentioned research, we synthesized and characterized the new dinuclear gold(III) complex with 1,5-naphthyridine as bridging ligand. The complex was fully characterized by UV-Vis, 1 H NMR spectroscopy, Cryospray-MS and molar conductivity.…”

The Therapeutic Potential in Cancer of Terpyridine‐Based Metal Complexes Featuring Group 11 Elements

“…The studies carried out with this complex revealed a decreasing reactivity trend among selected nucleophiles, with 5′‐GMP exhibiting the highest reactivity, followed by L–Met and GSH, implying that the guanine derivative is a more effective entering nucleophile than the studied S‐donor ligands. The complex displayed moderate binding affinities for both CT DNA and BSA, whereas molecular docking confirmed intercalation as the primary binding mode with DNA and identified the binding pocket at site I of BSA [42] …”

“…The complex displayed moderate binding affinities for both CT DNA and BSA, whereas molecular docking confirmed intercalation as the primary binding mode with DNA and identified the binding pocket at site I of BSA. [42] A distinct family of terpyridine-gold(III) complexes (Au5a-Au5c), featuring various 4'-phenyl substituents, exhibited remarkable cytotoxicity, surpassing cisplatin in multiple cancer cell lines. Notably, the corresponding ligands also demonstrated significant cytotoxicity against the tested cell lines.…”