Neuroprotective activity of 2-amino-1,3,4-thiadiazole derivative 4BrABT – an in vitro study

Małgorzata Juszczak 1, Katarzyna Walczak 2, Ewa Langner 2, Monika Karpińska 3, Joanna Matysiak 4, Wojciech Rzeski 5
1 - Department of Medical Biology, Institute of Rural Health, Lublin, Poland
2 - Department of Medical Biology, Institute of Rural Health, Lublin, Poland; Department of Pharmacology, Medical University, Lublin, Poland
3 - Institute of Industrial Organic Chemistry, Warsaw, Poland
4 - Department of Chemistry, University of Life Sciences, Lublin, Poland
5 - Department of Medical Biology, Institute of Rural Health, Lublin, Poland; Department of Virology and Immunology, Institute of Microbiology and Biotechnology, Maria Curie-Sklodowska University, Lublin, Poland
Ann Agric Environ Med
2013; 20 (3):
ICID: 1067443
Article type: Original article
 
 
4BrABT (2-(4-Bromophenylamino)-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole) is a compound known for its interesting in vitro anticancer profile. 4BrABT inhibited proliferation and motility of several cancer cell lines in concentrations which were not toxic to normal cells. A major problem associated with cancer chemotherapy, but also caused by environmental factors such as pesticides, is neurotoxicity. Therefore, the aim of the presented study was an in vitro evaluation of the neuroprotective activity of this compound. 4BrABT activity (1–100 μM) was tested in cultures of mouse neurons, rat astrocytes and rat oligodendrocytes. A possible protective action of the compound in different neurodegenerative models, as serum deprivation (SD), excitotoxicity (presence of 500 μM glutamate in culture medium), as well as cisplatin toxicity (astroglia – 50 μM and oligodendroglia – 100 μM) was investigated. Cell viability in the tested cultures was assessed with the use of LDH and MTT methods. Moreover, 4BrABT ability to prevent the cisplatin-induced apoptosis in astrocyte and oligodendrocyte cultures was analysed after Hoechst 33342 fluorostaining. The obtained results indicate that 4BrABT was not toxic to neurons, astrocytes and oligodendrocytes. Moreover, a decrease in the neuronal LDH level was observed, which may suggest the ability of 4BrABT to act as a trophic agent. Furthermore, the protective action of the studied compound was shown in neuronal cultures exposed to neurotoxic conditions (presence of glutamate and trophic stress) and in cisplatin-treated astrocytes and oligodendrocytes. The expression of anticancer and neuroprotective activity raises hopes for the potential use of 4BrABT as a safe anticancer drug, or neuroprotective agent in chemotherapy-associated neurotoxicity.
PMID 24069868 - click here to show this article in PubMed
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