title: Synthesis and cytotoxicity of some D-mannose click conjugates with aminobenzoic acid derivatives.
abstract: Two sets of new conjugates obtained from d-mannose derivatives and o-, m-, and p-substituted benzoic acid esters interconnected through a triazole ring were synthesized by Cu(I) catalyzed azide-alkyne cycloaddition. All synthesized compounds were tested for their in vitro cytotoxic activity against seven cancer cell lines with/without multidrug resistance phenotype as well as non-tumor MRC-5 and BJ fibroblasts. Butyl ester of 4-aminobenzoic acid 6c showed the highest activity among all tested compounds, however, it was active only against K562 myeloid leukemia cells. N-Glycosyltriazole conjugates, both acetylated and nonacetylated at mannose moiety, were almost completely inactive. In contrast, some of the acetylated O-glycosyl conjugates showed cytotoxic activity which was cell line dependent and strongly affected by position of benzoic acid substitution as well as a length of its ester alkyl chain; the most potent compound was acetylated mannoside conjugated with octyl ester of m-substituted benzoic acid. However, deacetylation resulting in hydrophilicity increase of the glycosides almost completely abolished their cytotoxic potency.
authors.affiliation: Department of Organic Chemistry, Palacky University, Tr. 17. listopadu 12, 771 46 Olomouc, Czech Republic.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Hradilová
authors.forename: Monika
authors.initials: M
authors.lastname: Poláková
authors.forename: Barbora
authors.initials: B
authors.lastname: Dvořáková
authors.forename: Marián
authors.initials: M
authors.lastname: Hajdúch
authors.forename: Ladislav
authors.initials: L
authors.lastname: Petruš
mesh_terms: D062365:Aminobenzoates / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D057930:Click Chemistry; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D008358:Mannose / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D062365:Aminobenzoates; D000970:Antineoplastic Agents; D008358:Mannose