title: Organoselenocyanates and symmetrical diselenides redox modulators: Design, synthesis and biological evaluation.
abstract: Oxidative stress (OS) and disturbed intracellular redox balance have been predominantly observed in different types of cancer, including hepatocellular carcinoma (HCC). Agents which can stop OS multi-stressor events and modulate the intracellular redox state are becoming a major focus in HCC prevention. Among them, compounds with glutathione peroxidase (GPx)-like activity are of particularly concern. We herein report the synthesis of novel series of organoselenocyanates and symmetrical diselenide antioxidants, inspired by the natural redox enzyme, GPx and the synthetic organoselenium ebselen antioxidants. Their cytotoxic activity was evaluated against Hep G2 cells and their antimicrobial activities were evaluated against Candida albicans (C. albicans) fungus as well as against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), gram-negative and gram-positive bacteria, respectively. These compounds were also tested for their antioxidant activities using 2,2-diphenyl-1-picrylhydrazyl (DPPH), GPx-like activity and bleomycin dependent DNA damage assays and a basic structure-activity relationship was subsequently established. The physicochemical parameters and drug-likeness were computed employing the Molinspiration online property calculation toolkit and MolSoft software. Interestingly, some compounds proved to be more cytotoxic than ebselen and the known anticancer drug 5-Fu and in the same time they showed similar, sometime even more, antifungal activity than the reference antifungal drugs. Among these compounds, compound 16 was considered to be the most interesting with free radical-scavenging activity comparable to ascorbic acid and a GPx-like activity similar to ebselen. As most of these compounds comply with Lipinski's Rule of Five, they promise good bioavailability, which needs to be studied as part of future investigations.
authors.affiliation: Organic Chemistry Division, Department of Chemistry, Faculty of Science, Mansoura University, El-Gomhorya Street, 35516 Mansoura, Egypt; Leibniz Institute of Plant Biochemistry, Department of Bioorganic Chemistry, Weinberg 3, D-06120 Halle (Saale), Germany. Electronic address: dr_saad_chem@mans.edu.eg.
authors.forename: Saad
authors.initials: S
authors.lastname: Shaaban
authors.affiliation: Biochemistry Division, Department of Chemistry, Faculty of Science, Mansoura University, El-Gomhorya Street, 35516 Mansoura, Egypt.
authors.forename: Amr
authors.initials: A
authors.lastname: Negm
authors.affiliation: Experimental Biology, Urology & Nephrology Center, Faculty of Medicine, Mansoura University, El-Gomhorya Street, 35516 Mansoura, Egypt.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Sobh
authors.affiliation: Leibniz Institute of Plant Biochemistry, Department of Bioorganic Chemistry, Weinberg 3, D-06120 Halle (Saale), Germany. Electronic address: wessjohann@ipb-halle.de.
authors.forename: Ludger A
authors.initials: LA
authors.lastname: Wessjohann
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002264:Carboxylic Acids / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D003485:Cyanates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D056945:Hep G2 Cells; D006801:Humans; D016566:Organoselenium Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010084:Oxidation-Reduction; D018036:Selenium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D000975:Antioxidants; D002264:Carboxylic Acids; D003485:Cyanates; D016566:Organoselenium Compounds; D018036:Selenium Compounds; C473453:seleninic acid; C053721:selenocyanic acid
keywords: Diselenides; Ebselen; GPx mimics; Multicomponent reactions; Organoselenocyanates