Synthesis and cytotoxicity of some d-mannose click conjugates with aminobenzoic acid derivatives
| Autor: | Ludmila Hradilová, Monika Poláková, Marian Hajduch, Ladislav Petruš, Barbora Dvořáková |
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| Rok vydání: | 2012 |
| Předmět: |
Stereochemistry
Drug Evaluation Preclinical Triazole Mannose Antineoplastic Agents Aminobenzoates Biochemistry Cell Line Analytical Chemistry Structure-Activity Relationship chemistry.chemical_compound Humans Structure–activity relationship Aminobenzoic acid Cell Proliferation Benzoic acid chemistry.chemical_classification Dose-Response Relationship Drug Molecular Structure Organic Chemistry Glycoside Stereoisomerism Biological activity General Medicine Fibroblasts chemistry Click Chemistry |
| Zdroj: | Carbohydrate Research. 361:1-6 |
| ISSN: | 0008-6215 |
| DOI: | 10.1016/j.carres.2012.08.001 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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