Synthesis of 5-[(1H-indol-3-yl)methyl]-1,3,4-oxadiazole-2(3H)-thiones and their protective activity against oxidative stress

0549797 - ÚEB 2022 RIV DE eng J - Journal Article
Iškauskienė, M. - Kadlecová, A. - Voller, J. - Janovská, Lucie - Malinauskienė, V. - Žukauskaitė, A. - Šačkus, A.
Synthesis of 5-[(1H-indol-3-yl)methyl]-1,3,4-oxadiazole-2(3H)-thiones and their protective activity against oxidative stress.
Archiv der Pharmazie. Roč. 354, č. 6 (2021), č. článku e2100001. ISSN 0365-6233. E-ISSN 1521-4184
Institutional support: RVO:61389030
Keywords : Caenorhabditis elegans * Friedreich's ataxia * indole * oxadiazole * oxidative stress
OECD category: Pharmacology and pharmacy
Impact factor: 4.613, year: 2021
Method of publishing: Open access
http://doi.org/10.1002/ardp.202100001

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.
Permanent Link: http://hdl.handle.net/11104/0325697