Sulforaphane homologues: Enantiodivergent synthesis of both enantiomers, activationof the Nrf2 transcription factor and selective cytotoxic activity
| Autor: | Inmaculada Fernández, Franziska Lieder, Noureddine Khiar, Sabine Werner, Miguel López-Lázaro, José Manuel Calderón-Montaño, Eleonora Elhalem, Rocío Recio |
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| Přispěvatelé: | Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica, Universidad de Sevilla. Departamento de Farmacología, Ministerio de Economía y Competitividad (MINECO). España, Junta de Andalucía |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Enantiodivergent synthesis
Stereochemistry NF-E2-Related Factor 2 chemistry.chemical_element R and S Sulforaphane and Homologues chemistry.chemical_compound Isothiocyanates Activation of Nrf2 factor Cell Line Tumor Drug Discovery Cytotoxic T cell Humans Transcription factor Pharmacology DAG-methodology Chiral auxiliary Cytotoxic activity Chemistry Organic Chemistry Stereoisomerism General Medicine respiratory system Sulfur Biochemistry Sulfoxides Isothiocyanate Epimer Enantiomer Drug Screening Assays Antitumor Sulforaphane |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname idUS. Depósito de Investigación de la Universidad de Sevilla |
| Popis: | Reported is an enantiodivergent approach for the synthesis of both enantiomers of sulforaphane (SFN) homologues with different chain lengths between the sulfinyl sulfur and the isothiocyanate groups and different substituents on the sulfinyl sulfur. The homologues were designed in order to unravel the effect of all the diversity elements included in sulforaphane's structure. The key step of the approach is the diastereoselective synthesis of both sulfinate ester epimers at sulfur, using as single chiral auxiliary the sugar derived diacetone-d-glucose. The approach allows the first synthesis of both enantiomers of 5-methylsulfinylpentyl isothiocyanate, and the biologically important 6-methylsulfinylhexyl isothiocyanate (6-HITC) found in Japanese horseradish, wasabi (Wasabia japonica). The ability of the synthesized compounds as inductors of phase II detoxifying enzymes has been studied by determining their ability to activate the cytoprotective transcription factor Nrf2. The cytotoxic activity of all the synthesized compounds against human lung adenocarcinoma (A549) and foetal lung fibroblasts (MRC-5) is also reported. Both enantiomers of sulforaphane and six homologues were obtained.The ability of the synthesized compounds to activate the Nrf2 is studied.The cytotoxic activity of the analogues against cancer and healthy cells is reported. |
| Databáze: | OpenAIRE |
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