RESEARCH PAPER
Neuroprotective activity of 2-amino-1,3,4-thiadiazole derivative 4BrABT – an in vitro study
 
More details
Hide details
1
Department of Medical Biology, Institute of Rural Health, Lublin, Poland
 
2
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 Virology and Immunology, Institute of Microbiology and Biotechnology, Maria Curie-Sklodowska University, Lublin, Poland
 
 
Corresponding author
Małgorzata Juszczak   

Department of Medical Biology, Institute of Rural Health, Lublin, Poland
 
 
Ann Agric Environ Med. 2013;20(3):575-579
 
KEYWORDS
ABSTRACT
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.
REFERENCES (22)
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. Environ Health. 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 the N-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 of excitotoxicity. 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 mediated by 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 in vivo 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 based compound. 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. Chem Pharm 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. Arzneimittelforschung 2008; 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 normal cells. 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 cerebellar granule neurons but not in astrocytes: in vitro paradigm of differential neurotoxicity. 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, Ikonomidou C. 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/5/7/2....
 
22.
Rzeski W, Pruskil S, Macke A, Felderhoff-Mueser U, Reiher AK, Hoerster F, Jansma C, Jarosz B, Stefanovska V, Bittigau P, Ikonomidou C. Anticancer agents are potent neurotoxins in vitro and in vivo. Ann Neurol. 2004; 56: 351–360.
 
eISSN:1898-2263
ISSN:1232-1966
Journals System - logo
Scroll to top