New gold pincer-type complexes: synthesis, characterization, DNA binding studies and cytotoxicity

Area of Science:

• Inorganic Chemistry
• Medicinal Chemistry
• Biochemistry

Background:

• Gold(III) compounds are being explored for their potential anticancer properties.
• Pincer ligands offer unique coordination environments for metal complexes.

Purpose of the Study:

• To synthesize and characterize novel monofunctional Au(III) complexes with pincer ligands.
• To evaluate their chemical stability, reactivity with biomolecules, and potential as antitumor agents.

Main Methods:

• Synthesis and characterization of three Au(III) complexes using elemental analysis and spectroscopic techniques (IR, UV-Vis, NMR, MALDI TOF MS).
• Assessment of chemical stability and reactivity with guanine derivatives and calf thymus DNA (CT DNA) using UV-Vis and stopped-flow spectroscopy.
• Investigation of DNA binding interactions via UV-Vis, fluorescence spectroscopy, viscosity measurements, and molecular docking.
• Evaluation of cytotoxicity against A549, A375, and LS-174 cell lines and mechanistic studies involving cell cycle, apoptosis, and reactive oxygen species (ROS).

Main Results:

• The synthesized Au(III) complexes ([Au(N-N'-N)Cl]Cl2) were stable under physiological conditions.
• Complexes exhibited moderate but differential reactivity with guanosine, 5'-GMP, and CT DNA, indicating an associative substitution mechanism.
• Complexes displayed moderate DNA binding affinity and stabilized the DNA duplex, with molecular docking suggesting intercalation.
• Complex 1 showed significant cytotoxicity (IC50 up to 20 μM) against tested cell lines, induced cell cycle perturbations and apoptosis in A375 cells, and affected ROS levels.

Conclusions:

• The novel Au(III) pincer complexes are stable and interact with DNA via intercalation.
• Complex 1 exhibits promising antitumor activity by inducing apoptosis and affecting ROS, warranting further investigation as a potential anticancer drug.