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

• Autorzy: Juszczak M. , Walczak K. , Langner E. , Karpinska M. , Matysiak J. , Rzeski W.
• Języki publikacji: EN

Abstrakty

EN

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.

• Wydawca: -
• Czasopismo: Annals of Agricultural and Environmental Medicine
• Rocznik: 2013
• Tom: 20
• Numer: 3
• Opis fizyczny: p.575-579,fig.,ref.

Twórcy

autor

Juszczak M.

• Department of Medical Biology, Institute of Rural Health, Lublin, Poland

autor

Walczak K.

• Department of Medical Biology, Institute of Rural Health, Lublin, Poland; Department of Pharmacology, Medical University, Lublin, Poland

autor

Langner E.

• Department of Medical Biology, Institute of Rural Health, Lublin, Poland; Department of Pharmacology, Medical University, Lublin, Poland

autor

Karpinska M.

• Institute of Industrial Organic Chemistry, Warsaw, Poland

autor

Matysiak J.

• Department of Chemistry, University of Life Sciences, Lublin, Poland

autor

Rzeski W.

• 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

Bibliografia

• 1. Swerdlow RH. Pathogenesis of Alzheimer’s disease. Clin Interv Aging. 2007; 2: 347–359.
• 2. Fahn S, Sulzer D. Neurodegeneration and neuroprotection in Parckinson Disease. Neuro Rx. 2004; 1: 139–154.
• 3. Sioka C, Kyritsis AP. Central and peripheral nervous system toxicity of common chemotherapeutic agents. Cancer Chemother Pharmacol. 2009; 63: 761–767.
• 4. Kelsey NA, Wilkins HM, Linseman DA. Nutraceutical antioxidants as novel neuroprotective agents. Molecules. 2010; 15: 7792–7814.
• 5. Costa LG, Giordano G, Guizzetti M, Vitalone A. Neurotoxicity of pesticides: a brief review. Front Biosci. 2008; 1(13): 1240–1249.
• 6. Alavanja MC, Hoppin JA, Kamel F. Health effects of chronic pesticide exposure: cancer and neurotoxicity. Annu Rev Public Health. 2004;25: 155- 197.
• 7. Bjorling-Poulsen M, Andersen HR, Grandjean P. Potential developmental neurotoxicity of pesticides used in Europe. EnvironHealth. 2008 Oct 22; 7: 50.
• 8. Weaver CE Jr, Marek P, Park-Chung M, Tam SW, Farb DH. Neuroprotective activity of a new class of steroidal inhibitors of theN-methyl-D-aspartate receptor. Proc Natl Acad Sci. USA 1997; 94:10450–10454.
• 9. Volbracht C, Beek J, Zhu C, Blomgren K, Leist M. Neuroprotective properties of memantine in different in vitro and in vivo models ofexcitotoxicity. Eur J Neurosci. 2006; 23: 2611–2622.
• 10. Bruno V, Battaglia G, Casabona G, Copani A, Caciagli F, Nicoletti F. Neuroprotection by glial metabotropic glutamate receptors is mediatedby Transforming Growth Factor-b. J Neurosci 1998; 18: 9594–9600.
• 11. Dejda A, Sokołowska P, Nowak JZ. Neuroprotective potential of three neuropeptides PACAP, VIP and PHI. Pharmacol Rep. 2005; 57: 307–320.
• 12. Shimazawa M, Chikamatsu S, Morimoto N, Mishima S, Nagai H, Hara H. Neuroprotection by brazilian green propolis against in vitro and invivo ischemic neuronal damage. eCAM 2005; 2: 201–207.
• 13. Rzeski W, Matysiak J, Kandefer-Szerszeń M. Anticancer, neuroprotective activities and computational studies of 2-amino-1,3,4-thiadiazole basedcompound. Bioorg Med Chem. 2007; 15: 3201–3207.
• 14. Matysiak J, Opolski A. Synthesis and antiproliferative activity of N-substituted 2-amino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles.Bioorg Med Chem. 2006; 14: 4483–4489.
• 15. Matysiak J. Evaluation of antiproliferative effect in vitro of same 2-amino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole derivatives. ChemPharm Bull. 2006; 54: 988–991.
• 16. Juszczak M, Matysiak J, Brzana W, Niewiadomy A, Rzeski W. Evaluation of the antiproliferative activity of 2-(monohalogenophenyl-amino)-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles. Arzneimittelforschung2008; 58: 353–357.
• 17. Juszczak M, Matysiak J, Niewiadomy A, Rzeski W. The activity of a new 2-amino-1,3,4-thiadiazole derivative 4ClABT in cancer and normalcells. Folia Histochem. Cytobiol. 2011; 49(3): 436–444.
• 18. Lu K, Loo TL. The pharmacologic fate of the antitumor agent 2-amino- 1,3,4-thiadiazole in the dog. Cancer Chemother Pharmacol. 1980; 4:275–279.
• 19. Wick A, Wick W, Hirrlinger J, Gerhart E, Dringen R, Dichans J, Weller M, Schulz JB. Chemotherapy-induced cell death in primary cerebellargranule neurons but not in astrocytes: in vitro paradigm of differentialneurotoxicity. J Neurochem. 2004; 91: 1067–1074.
• 20. Stepulak A, Luksch H, Gebhardt C, Uckermann O, Marzahn J, Sifringer M, Rzeski W, Staufner C, Brocke KS, Turski L, IkonomidouC. Expression of glutamate receptor subunits in human cancers.Histochem Cell Biol. 2009; 132: 435–445.
• 21. Dietrich J, Han R, Yang Y, Mayer-Pröschel M, Noble M. CNS progenitor cells and oligodendrocytes are targets of chemotherapeutic agents in vitro and in vivo. J Biol. 2006; 5: 22: doi:10.1186/jbiol50, http://jbiol.com/content/5/7/22.
• 22. Rzeski W, Pruskil S, Macke A, Felderhoff-Mueser U, Reiher AK, Hoerster F, Jansma C, Jarosz B, Stefanovska V, Bittigau P, IkonomidouC. Anticancer agents are potent neurotoxins in vitro and in vivo. AnnNeurol. 2004; 56: 351–360.

Uwagi

rekord w opracowaniu