Natural-Antioxidant-Inspired Benzo[b]selenophenes: Synthesis, Redox Properties, and Antiproliferative Activity

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Chemical Biology

Background:

• Benzo[b]selenophenes are heterocyclic compounds with diverse biological activities.
• Developing efficient synthetic routes for substituted benzo[b]selenophenes is crucial for exploring their potential applications.
• Understanding structure-activity relationships (SARs) is key to optimizing drug candidates.

Purpose of the Study:

• To establish a general synthetic pathway for polyhydroxy-2- and -3-arylbenzo[b]selenophenes.
• To investigate the redox properties, free-radical-scavenging ability, and cytotoxicity of the synthesized compounds.
• To elucidate the SARs governing the biological activities, particularly peroxyl-radical scavenging.

Main Methods:

• Cyclization of arylalkynes under selenobromination conditions.
• Acid-induced 3,2-aryl shift for regioselective synthesis.
• Evaluation of antioxidant capacity using free-radical scavenging assays.
• Assessment of cytotoxicity against a panel of human and murine malignant cell lines (MCF-7, MDA-MB-231, HepG2, 4T1).

Main Results:

• A general synthetic route was developed for polyhydroxy-2- and -3-arylbenzo[b]selenophenes from common precursors.
• The synthesized compounds exhibited varying degrees of redox properties and free-radical-scavenging activity.
• Cytotoxicity varied across different cancer cell lines, with some compounds showing significant potency.
• Key structural features responsible for potent peroxyl-radical scavenging were identified.

Conclusions:

• The developed synthetic methodology provides access to a novel class of polyhydroxyarylbenzo[b]selenophenes.
• The study highlights the potential of these compounds as antioxidants.
• SAR analysis provides valuable insights for the rational design of more potent radical scavengers and potential therapeutic agents.