title: Sulfur, selenium and tellurium pseudopeptides: synthesis and biological evaluation.
abstract: A new series of sulfur, selenium and tellurium peptidomimetic compounds was prepared employing the Passerini and Ugi isocyanide based multicomponent reactions (IMCRs). These reactions were clearly superior to conventional methods traditionally used for organoselenium and organotellurium synthesis, such as classical nucleophilic substitution and coupling methods. From the biological point of view, these compounds are of considerable interest because of suspected anticancer and antimicrobial activities. While the sulfur and selenium containing compounds generally did not show either anticancer or antimicrobial activities, their tellurium based counterparts frequently exhibited antimicrobial activity and were also cytotoxic. Some of the compounds synthesized even showed selective activity against certain cancer cells in cell culture. These compounds induced a cell cycle delay in the G0/G1 phase. At closer inspection, the ER and the actin cytoskeleton appeared to be the primary cellular targets of these tellurium compounds, in line with some of our previous studies. As most of these peptidomimetic compounds also comply with Lipinski's Rule of Five, they promise good bioavailability, which needs to be studied as part of future investigations.
authors.affiliation: Department of Chemistry, Faculty of Science, Mansoura University, El-Gomhoria Street, Mansoura 35516, Egypt; Department of Chemical Biology, Helmholtz Centre for Infection Research, Inhoffenstraße 7, D-38124 Braunschweig, Germany; Division of Bioorganic Chemistry, School of Pharmacy, Saarland University, D-66123 Saarbruecken, Germany.
authors.forename: Saad
authors.initials: S
authors.lastname: Shaaban
authors.affiliation: Department of Chemical Biology, Helmholtz Centre for Infection Research, Inhoffenstraße 7, D-38124 Braunschweig, Germany. Electronic address: florenz.sasse@helmholtz-hzi.de.
authors.forename: Florenz
authors.initials: F
authors.lastname: Sasse
authors.affiliation: Division of Bioorganic Chemistry, School of Pharmacy, Saarland University, D-66123 Saarbruecken, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Burkholz
authors.affiliation: Division of Bioorganic Chemistry, School of Pharmacy, Saarland University, D-66123 Saarbruecken, Germany. Electronic address: c.jacob@mx.uni-saarland.de.
authors.forename: Claus
authors.initials: C
authors.lastname: Jacob
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000254:growth & development; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005658:Fungi / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D061986:MCF-7 Cells; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry; D057786:Peptidomimetics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012643:Selenium / Q000737:chemistry; D013329:Structure-Activity Relationship; D013455:Sulfur / Q000737:chemistry; D013691:Tellurium / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D000970:Antineoplastic Agents; D010455:Peptides; D057786:Peptidomimetics; D013455:Sulfur; D012643:Selenium; D013691:Tellurium
keywords: Anticancer activity; Antimicrobial activity; Isonitrile based multicomponent reactions (IMCR); Lipinski’s Rule of Five; Redox-modulation; Tellurium