Expeditious Entry to Functionalized Pseudo-peptidic Organoselenide Redox Modulators via Sequential Ugi/SN Methodology

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Pharmacology

Background:

• Organoselenium compounds are recognized for diverse biological activities.
• Developing novel selenium-containing molecules is crucial for drug discovery.
• Efficient synthetic strategies are needed for complex organoselenium structures.

Purpose of the Study:

• To synthesize novel symmetrical diselenide and selenium-containing quinone pseudopeptides.
• To evaluate the antimicrobial and anticancer properties of the synthesized compounds.
• To assess the antioxidant and pro-oxidant profiles of these organoselenides.

Main Methods:

• Employed a one-pot Ugi reaction followed by sequential nucleophilic substitution (SN).
• Assessed antimicrobial activity against bacteria and fungi.
• Evaluated anticancer activity against MCF-7 and HepG2 cell lines.
• Determined antioxidant/pro-oxidant status using DPPH, bleomycin-dependent DNA damage, and GPx-like activity assays.

Main Results:

• Selenium-based quinones demonstrated potent cytotoxicity, particularly against MCF-7 cells.
• Symmetrical diselenides displayed superior glutathione peroxidase (GPx)-like activity compared to ebselen.
• Compounds 7, 8, 9, and 10 showed significant antifungal activity comparable to clotrimazole and modest antibacterial effects against S. aureus.

Conclusions:

• The developed synthetic route efficiently produces selenium-containing pseudopeptides.
• Synthesized organoselenides act as redox-modulating agents.
• These compounds exhibit promising potential as anticancer and antifungal agents.