DNA/protein binding, molecular docking, and in vitro anticancer activity of some thioether-dipyrrinato complexes

Area of Science:

• Coordination Chemistry
• Organometallic Chemistry
• Medicinal Inorganic Chemistry

Background:

• Synthesis and characterization of novel metal complexes are crucial for developing new therapeutic agents.
• Understanding the interaction of metal complexes with biological targets like DNA and proteins is key to their medicinal applications.

Purpose of the Study:

• To synthesize and characterize arene ruthenium, rhodium, and iridium complexes with a 5-(4-methylthiophenyl)dipyrromethene ligand.
• To investigate the DNA-binding, cytotoxic, and protein-interaction properties of these novel metal complexes.
• To evaluate their potential as anticancer agents against Dalton's lymphoma cell line.

Main Methods:

• Complex synthesis and characterization using elemental analysis, ESI-MS, FT-IR, NMR, UV/vis, emission spectroscopy, and electrochemistry.
• DNA-binding studies using UV/vis absorption, fluorescence quenching, and molecular docking.
• Cytotoxicity evaluation via MTT assay, AO/EtBr staining, and DNA ladder assay.
• Bovine serum albumin (BSA) interaction studies through fluorescence quenching.

Main Results:

• Four metal complexes (1-4) were successfully synthesized and fully characterized.
• Complexes 1-4 demonstrated effective binding to calf thymus DNA (CT DNA) via intercalation and electrostatic interactions.
• Significant in vitro cytotoxicity against Dalton's lymphoma (DL) cells was observed, with an activity order of 2 > 1 > 4 > 3.
• Complexes induced apoptosis and morphological changes in DL cells, and quenched BSA fluorescence, indicating protein interaction.

Conclusions:

• The synthesized ruthenium, rhodium, and iridium complexes exhibit promising anticancer properties.
• Their mechanism of action involves DNA binding and interaction with proteins, leading to apoptosis in cancer cells.
• Complex 2, a ruthenium complex, showed the highest cytotoxicity, suggesting potential for further development as an anticancer therapeutic.