Synthesis of 5-[(1H-indol-3-yl)methyl]-1,3,4-oxadiazole-2(3H)-thiones and their protective activity against oxidative stress
Language English Country Germany Media print-electronic
Document type Journal Article
Grant support
LTC18078
Ministry of Education, Youth and Sports of the Czech Republic (program INTER-COST)
LTC19030
Ministry of Education, Youth and Sports of the Czech Republic (program INTER-COST)
CZ.02.1.01/0.0/0.0/16_019/0000868
European Regional Development Fund
- Keywords
- Caenorhabditis elegans, Friedreich's ataxia, indole, oxadiazole, oxidative stress,
- MeSH
- Acetates chemical synthesis MeSH
- Antioxidants * chemical synthesis chemistry pharmacology MeSH
- Caenorhabditis elegans MeSH
- Friedreich Ataxia drug therapy metabolism pathology MeSH
- Indoles * chemistry pharmacology MeSH
- Cells, Cultured MeSH
- Indoleacetic Acids chemistry MeSH
- Humans MeSH
- Oxadiazoles * chemical synthesis chemistry pharmacology MeSH
- Oxidative Stress drug effects MeSH
- Thiones * chemical synthesis chemistry pharmacology MeSH
- Structure-Activity Relationship MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Acetates MeSH
- Antioxidants * MeSH
- indole MeSH Browser
- indoleacetic acid MeSH Browser
- Indoles * MeSH
- Indoleacetic Acids MeSH
- Oxadiazoles * MeSH
- Thiones * MeSH
A small library of 2-[(1H-indol-3-yl)methyl]-5-(alkylthio)-1,3,4-oxadiazoles was prepared, starting from indole-3-acetic acid methyl ester and its 5-methyl-substituted derivative. The synthetic route involved the formation of intermediate hydrazides, their condensation with carbon disulfide, and intramolecular cyclization to corresponding 5-[(1H-indol-3-yl)methyl]-1,3,4-oxadiazole-2(3H)-thiones. The latter were then S-alkylated, and in case of ester derivatives, they were further hydrolyzed into corresponding carboxylic acids. All 5-[(1H-indol-3-yl)methyl]-1,3,4-oxadiazole-2(3H)-thiones and their S-alkylated derivatives were then screened for their protective effects in vitro and in vivo. Methyl substitution on the indole ring and propyl, butyl, or benzyl substitution on sulfhydryl group-possessing compounds were revealed to protect Friedreich's ataxia fibroblasts against the effects of glutathione depletion induced by the γ-glutamylcysteine synthetase inhibitor, buthionine sulfoximine. Two of the active compounds also reproducibly increased the survival of Caenorhabditis elegans exposed to juglone-induced oxidative stress.
Department of Chemical Biology Faculty of Science Palacký University Olomouc Czech Republic
Department of Experimental Biology Faculty of Science Palacký University Olomouc Czech Republic
Department of Organic Chemistry Kaunas University of Technology Kaunas Lithuania
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