Chalcogen-containing phenolics as antiproliferative agents.

Area of Science:

• Medicinal Chemistry
• Organic Chemistry
• Biochemistry

Background:

• The rising incidence of cancer necessitates the development of innovative therapeutic strategies.
• Combining bioactive polyphenolic structures with organoselenium compounds presents a promising avenue for novel drug discovery.

Purpose of the Study:

• To synthesize and evaluate novel organoselenium compounds with potential antiproliferative properties.
• To investigate the structure-activity relationships of these compounds and their mechanisms of action.

Main Methods:

• Synthesis of four distinct families of compounds, including isothiocyanates, thioureas, and their selenium isosters, derived from dopamine, norepinephrine, and epinephrine.
• Assessment of antiproliferative activity using GI50 values and cell cycle assays.
• Evaluation of antiradical and glutathione peroxidase-like activities.
• Redox analysis on HeLa cells to determine reactive oxygen species (ROS) levels.

Main Results:

• Heterocumulenes derived from dopamine and β-O-methylnoradrenaline demonstrated significant antiproliferative effects (GI50 < 10 μM).
• Selenoureas, particularly those with electron-withdrawing groups on the phenyl ring, exhibited strong antiproliferative, antiradical, and glutathione peroxidase-like activities.
• Compounds showed up to a 14-fold increase in activity compared to classical chemotherapeutic agents, with distinct mechanisms of action.
• Incubation with these compounds led to increased ROS levels in HeLa cells.

Conclusions:

• The synergistic combination of organoselenium and phenolic moieties yields compounds with significant antiproliferative potential.
• These novel compounds represent valuable lead structures for the development of new anticancer agents.
• The observed increase in ROS suggests a potential mechanism for their cytotoxic effects.