Biomolecular Interactions and Anticancer Mechanisms of Ru(II)-Arene Complexes of Cinnamaldehyde-Derived Thiosemicarbazone Ligands: Analysis Combining In Silico and In Vitro Approaches.
Vishnunarayanan Namboothiri Vadakkedathu PalakkeezhillamJebiti HaribabuVaishnu Suresh KumarVipin ManakkadanPuthiyavalappil RasinJuan Pablo MuenaMahendiran DharmasivamAnandaram SreekanthPublished in: ACS applied bio materials (2024)
Our study focuses on synthesizing and exploring the potential of three N-(4) substituted thiosemicarbazones derived from cinnamic aldehyde, alongside their Ru(II)-(η 6 -p-cymene)/(η 6 -benzene) complexes. The synthesized compounds were comprehensively characterized using a range of analytical techniques, including FT-IR, UV-visible spectroscopy, NMR ( 1 H, 13 C), and HRMS. We investigated their electronic and physicochemical properties via density functional theory (DFT). X-ray crystal structures validated structural differences identified by DFT. Molecular docking predicted promising bioactivities, supported by experimental observations. Notably, docking with EGFR suggested an inhibitory potential against this cancer-related protein. Spectroscopic titrations revealed significant DNA/BSA binding affinities, particularly with DNA intercalation and BSA hydrophobic interactions. RuPCAM displayed the strongest binding affinity with DNA (K b = 6.23 × 10 7 M -1 ) and BSA (K b = 9.75 × 10 5 M -1 ). Assessed the cytotoxicity of the complexes on cervical cancer cells (HeLa), and breast cancer cells (MCF-7 and MDA-MB 231), revealing remarkable potency. Additionally, selectivity was assessed by examining MCF-10a normal cell lines. The active complexes were found to trigger apoptosis, a vital cellular process crucial for evaluating their potential as anticancer agents utilizing staining assays and flow cytometry analysis. Intriguingly, complexation with Ru(II)-arene precursors significantly amplified the bioactivity of thiosemicarbazones, unveiling promising avenues toward the creation of powerful anticancer agents.
Keyphrases
- molecular docking
- breast cancer cells
- density functional theory
- molecular dynamics simulations
- flow cytometry
- single molecule
- circulating tumor
- molecular dynamics
- high resolution
- cell free
- small cell lung cancer
- cell cycle arrest
- magnetic resonance
- cell death
- oxidative stress
- tyrosine kinase
- water soluble
- energy transfer
- endoplasmic reticulum stress
- binding protein
- single cell
- dna binding
- computed tomography
- ionic liquid
- data analysis
- capillary electrophoresis