Synthesis, Characterization, DNA/HSA Interaction, and Cytotoxic Activity of a Copper(II) Thiolate Schiff Base Complex and Its Corresponding Water-Soluble Stable Sulfinato-O Complex Containing Imidazole as a Co-ligand.
Kumudini PaliwalParamita HaldarP K Sudhadevi AntharjanamManjuri KumarPublished in: ACS omega (2023)
A Cu(II) thiolato complex [CuL( imz )] ( 1 ) (H 2 L = o -HOC 6 H 4 C(H)=NC 6 H 4 SH- o ) and the corresponding water-soluble stable sulfinato-O complex [CuL'( imz )] ( 2 ) (H 2 L' = o -HOC 6 H 4 C(H)=NC 6 H 4 S(=O)OH) were synthesized and characterized using physicochemical techniques. Compound 2 is found to be a dimer in the solid state as characterized using single-crystal X-ray crystallography. XPS studies clearly showed the differences in the sulfur oxidation states in 1 and 2 . Both compounds are found to be monomers in solution as revealed from their four-line X-band electron paramagnetic resonance spectra in CH 3 CN at room temperature (RT). 1-2 were tested to assess their ability to exhibit DNA binding and cleavage activity. Spectroscopic studies and viscosity experiments suggest that 1-2 bind to CT-DNA through the intercalation mode having moderate binding affinity ( K b ∼ 10 4 M -1 ). This is further supported by molecular docking studies of complex 2 with CT-DNA. Both complexes display significant oxidative cleavage of pUC19 DNA. Complex 2 also showed hydrolytic DNA cleavage. The interaction of 1-2 with HSA revealed that they have strong ability to quench the intrinsic fluorescence of HSA by a static quenching mechanism ( k q ∼ 10 13 M -1 s -1 ). This is further complemented by Förster resonance energy transfer studies that revealed binding distances of r = 2.85 and 2.75 nm for 1 and 2 , respectively, indicating high potential for energy transfer from HSA to complex. 1-2 were capable of inducing conformational changes of HSA at secondary and tertiary levels as observed from synchronous and three-dimensional fluorescence spectroscopy. Molecular docking studies with 2 indicate that it forms strong hydrogen bonds with Gln221 and Arg222 located near the entrance of site-I of HSA. 1-2 showed potential toxicity in human cervical cancer HeLa cells, lung cancer A549 cells, and cisplatin-resistant breast cancer MDA-MB-231 cells and appeared to be most potent against HeLa cells (IC 50 = 2.04 μM for 1 and 1.86 μM for 2 ). In HeLa cells, 1-2 mediated cell cycle arrest in S and G2/M phases, which progressed into apoptosis. Apoptotic features seen from Hoechst and AO/PI staining, damaged cytoskeleton actin viewed from phalloidin staining, and increased caspase-3 activity upon treatment with 1-2 collectively suggested that they induced apoptosis in HeLa cells via caspase activation. This is further supported by western blot analysis of the protein sample extracted from HeLa cells treated with 2 .
Keyphrases
- cell cycle arrest
- induced apoptosis
- cell death
- energy transfer
- pi k akt
- endoplasmic reticulum stress
- molecular docking
- oxidative stress
- signaling pathway
- dna binding
- single molecule
- room temperature
- squamous cell carcinoma
- small molecule
- computed tomography
- quantum dots
- cell proliferation
- ionic liquid
- climate change
- high resolution
- risk assessment
- young adults
- single cell
- endothelial cells
- image quality
- breast cancer cells
- cell migration
- high intensity