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2-Amino-5-alkylidenethiazol-4-ones as promising lipid peroxidation inhibitors

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Abstract

2-Amino-5-alkylidenethiazol-4-one represents a promising scaffold in medicinal chemistry and drug discovery. In the present study the antioxidant activity of 30 diverse 2-amino-5-alkylidenethiazol-4-ones was screened using a lipid peroxidation (LP) method. All compounds under study showed activity regardless of the substituent nature. However, several compounds exhibited a significant LP inhibition effect, which was in the range of that obtained with standard antioxidants. Compounds containing an (indol-3-yl)methylene group at position 5 of thiazol-4-one moiety and a six-membered ring as the 2-amino substituent showed inhibitory effects higher than 60 %. The most active compound, 5-benzylidene-2-morpholinothiazol-4(5H)-one, was investigated by means of ab initio calculations in order to clarify the most probable mechanism of antioxidant action. These calculations imply that electron transfer from the 2-amino-5-alkylidenethiazol-4-ones to the lipid alkoxyl, lipid peroxyl, or hydroxyl radicals could produce radical cations able to scavenge the lipid radicals and produce adducts, and ultimately terminate the reaction by proton transfer. Thus we propose the electron transfer (SET) mechanism as the most probable one that explains the observed inhibition of LP.

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Acknowledgments

The financial support of this work by Ministry of Education, Science and Technological Development of the Republic of Serbia (Grants No. OI-172044 and TR-34012), Slovenian Research Agency (Grant No. P1-0208), and National Science Fund of Bulgaria (Contract RNF01/0110) is gratefully acknowledged.

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Authors and Affiliations

  1. Faculty of Technology, University of Niš, Bulevar oslobodjenja 124, 16000, Leskovac, Serbia

    Jelena Zvezdanovic, Dragan Cvetkovic & Dejan Markovic

  2. Institute of Organic Chemistry and Centre of Phytochemistry, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Build. 9, 1113, Sofia, Bulgaria

    Lalka Daskalova & Denitsa Yancheva

  3. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000, Ljubljana, Slovenia

    Marko Anderluh

  4. Department of Chemistry, Faculty of Medicine, University of Niš, Bulevar Dr Zorana Djindjica 81, 18000, Niš, Serbia

    Andrija Smelcerovic

Authors
  1. Jelena Zvezdanovic
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  2. Lalka Daskalova
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  3. Denitsa Yancheva
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  4. Dragan Cvetkovic
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  5. Dejan Markovic
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  6. Marko Anderluh
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  7. Andrija Smelcerovic
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Correspondence to Marko Anderluh or Andrija Smelcerovic.

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Zvezdanovic, J., Daskalova, L., Yancheva, D. et al. 2-Amino-5-alkylidenethiazol-4-ones as promising lipid peroxidation inhibitors. Monatsh Chem 145, 945–952 (2014). https://doi.org/10.1007/s00706-014-1162-4

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  • DOI: https://doi.org/10.1007/s00706-014-1162-4

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