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Synthesis and biological activity of 4-amino-3-chloro-1H-pyrrole-2,5-diones

  • Halyna M. KuznietsovaEmail author
  • Vasyl V. Hurmach
  • Andriy V. Bychko
  • Olena I. Tykhoniuk
  • Demyd S. Milokhov
  • Olga V. Khilya
  • Yulian M. Volovenko
  • Volodymyr K. Rybalchenko
Original Research
  • 12 Downloads

Abstract

4-Amino-3-chloro-1H-pyrrole-2,5-dione derivatives were designed and synthesized as potential tyrosine kinase inhibitors. One of them has been shown to inhibit growth of cancer cell lines and in vivo tumors. To determine the impact of side groups on biological activity the ability of different 4-amino-3-chloro-1H-pyrrole-2,5-diones to interact with ATP-binding domains of growth factor receptors and with model cell membranes were aimed to be discovered. The methods of molecular docking, short-molecular dynamics (in silico) and non-steady cyclic current–voltage characteristics (in vitro) were used. Five 4-amino-3-chloro-1H-pyrrole-2,5-diones were synthesized from 3,4-dichloro-1H-pyrrole-2,5-diones. All of them demonstrated the potential ability to form complexes with ATP-binding domains of EGFR and VEGFR2. These complexes were more stable compared to those with ANP. 4-Amino-3-chloro-1H-pyrrole-2,5-diones while interact with different bilayer lipid membranes caused an increase of their specific conductance and electric capacity, demonstrating the certain disturbance in lipid packing. Obtained data allowed us to suggest that proposed chemicals can interact with the surface of lipid bilayer, do likely intercalate into the membrane and form stable complexes with EGFR and VEGFR2. So, the prospect of developed chemicals to be effective EGFR and VEGFR2 inhibitors and therefore realize antitumor activity was concluded.

Keywords

4-Amino-3-chloro-1H-pyrrole-2 5-Dione derivatives EGFR VEGFR2 Bilayer lipid membranes Cyclic current–voltage characteristics 

Notes

Acknowledgements

The research was carried out in the frame of the Fundamental research grants of Ministry of Education and Science of Ukraine No. 0118U000244 and No. 19BP07-03.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest regarding the publication of this paper.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Halyna M. Kuznietsova
    • 1
    Email author
  • Vasyl V. Hurmach
    • 1
  • Andriy V. Bychko
    • 2
  • Olena I. Tykhoniuk
    • 1
  • Demyd S. Milokhov
    • 1
  • Olga V. Khilya
    • 1
  • Yulian M. Volovenko
    • 1
  • Volodymyr K. Rybalchenko
    • 1
  1. 1.Taras Shevchenko National University of KyivKievUkraine
  2. 2.Bogomolets National Medical UniversityKievUkraine

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