title: Synthesis and biological evaluation of a new class of glycoconjugated disulfides that exhibit potential anticancer properties.
abstract: A synthetic strategy, based on the in situ generation of sulfenic acids and their thermolysis in the presence of thiols, was developed for obtaining a collection of polyvalent disulfides in which a benzene scaffold accommodates two or three flexible arms connecting saccharide moieties. Targeting carbohydrate metabolism or carbohydrate-binding proteins may constitute important approaches in the discovery process of new therapeutic anticancer agents. Therefore, a preliminary screening to ascertain the cytostatic/cytotoxic potential of this new class of enantiopure glycoconjugated disulfides has been conducted. Among them, products with two disulfide arms, harbouring galactose rings, induced high levels of apoptosis on U937 histiocytic lymphoma cells, but lower levels of cell death on peripheral blood mononuclear cells from healthy donors. Further experiments indicated that apoptosis induced by these glycoconjugated bis(disulfides) in U937 cells corresponds to the Bcl-2-sensitive, intrinsic form of apoptotic cell death. The bioinvestigation was extended to a panel of human cancer cell lines with different levels of malignancy and resistance to chemotherapeutic agents. Compounds under study proved to induce detectable levels of cell death towards all the tested cancer cell lines.
authors.affiliation: Dipartimento di Chimica Organica e Biologica, Università degli Studi di Messina, Viale Ferdinando Stagno d'Alcontres 31 (vill. S. Agata), 98166 Messina, Italy. paola.bonaccorsi@unime.it
authors.forename: Paola
authors.initials: P
authors.lastname: Bonaccorsi
authors.forename: Francesca
authors.initials: F
authors.lastname: Marino-Merlo
authors.forename: Anna
authors.initials: A
authors.lastname: Barattucci
authors.forename: Gianluca
authors.initials: G
authors.lastname: Battaglia
authors.forename: Emanuela
authors.initials: E
authors.lastname: Papaianni
authors.forename: Teresa
authors.initials: T
authors.lastname: Papalia
authors.forename: Maria C
authors.initials: MC
authors.lastname: Aversa
authors.forename: Antonio
authors.initials: A
authors.lastname: Mastino
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002240:Carbohydrate Sequence; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004220:Disulfides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006001:Glycoconjugates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D015394:Molecular Structure; D020298:U937 Cells
chemical_list: D000970:Antineoplastic Agents; D004220:Disulfides; D006001:Glycoconjugates