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

Author(s):

Saad Shaaban, Amr Negm, Mohamed A. Sobh and Ludger A. Wessjohann   Pages 621 - 632 ( 12 )

Abstract:

An efficient route towards the synthesis of symmetrical diselenide and seleniumcontaining quinone pseudopeptides via one-pot Ugi and sequential nucleophilic substitution (SN) methodology was developed. Compounds were evaluated for their antimicrobial and anticancer activities and their corresponding antioxidant/pro-oxidant profiles were assesed employing 2,2-diphenyl-1-picrylhydrazyl (DPPH), bleomycin dependent DNA damage and glutathione peroxidase (GPx)-like activity assays. Selenium based quinones were among the most potent cytotoxic compounds with a slight preference for MCF-7 compared to HepG2 cells and good free radical scavenging activity. Furthermore, symmetrical diselenides exhibited the most potent GPx-like activity compared to ebselen. Moreover, compounds 7, 8, 9 and 10 exhibited similar antifungal activity to the antifungal drug clotrimazole with modest activity against the Gram-positive bacterium S. aureus. These results indicate that some of the synthesized organoselenides are redox modulating agent with promising anti-cancer and antifungal potentials.

Keywords:

Anticancer; diselenides, diversity-oriented synthesis (DOS), glutathione peroxidase mimics, isocyanide-based multicomponent reactions (IMCR), pseudopeptides, selenium-based quinones, Ugi reaction.

Affiliation:

Organic Chemistry Division, Department of Chemistry, Faculty of Science, Mansoura University, El-Gomhorya Street, 35516 Mansoura, Egypt.

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