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Medicinal Chemistry Research

, Volume 28, Issue 12, pp 2252–2261 | Cite as

Synthesis of novel benzimidazole–oxadiazole derivatives as potent anticancer activity

  • Ulviye Acar ÇevikEmail author
  • Derya Osmaniye
  • Betül Kaya Çavuşoğlu
  • Begüm Nurpelin Sağlik
  • Serkan Levent
  • Sinem Ilgin
  • Nafiz Öncü Can
  • Yusuf Özkay
  • Zafer Asım Kaplancikli
Original Research
  • 140 Downloads

Abstract

DNA topoisomerase I regulates DNA topological structure in many cellular metabolic processes and is a validated target for the development of antitumor agents. In this work, a series of novel 2-[(5-(4-(5(6)-substituted-1H-benzimidazol-2-yl)phenyl)-1,3,4-oxadiazol-2-yl)thio]-1-(4-substitutedphenyl)ethan-1-ones (4a–4s) derivatives have been synthesized and evaluated for DNA Topo I inhibition and cytotoxicity. The structures of the compounds (4a–4s) were confirmed by IR, 1H-NMR, 13C-NMR, 2D NMR, and mass spectroscopy. Anticancer activity of these compounds was assessed against two different human cancer cell lines A549 (human lung adenocarcinoma) and HepG2 (human liver cancer cell line), as well as normal mouse embryonic fibroblast cells (NIH3T3). IC50 values of compounds 4a, 4c, and 4f were highest than those exhibited for the reference drug cisplatin. Then, the inhibitory effect of 4a, 4c, and 4f compounds on topoisomerase I enzyme with the relaxation assay was investigated on supercoiled DNA using agarose gel electrophoresis. The Annexin V-FITC assay demonstrated that these compounds induce cell death by apoptosis.

Keywords

Benzimidazole 1,3,4-Oxadiazole Anticancer DNA flow cytometric 2D NMR 

Notes

Acknowledgements

This study was financially supported by Anadolu University Scientific Research Projects Commission, Project no. 1602S065.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

44_2019_2451_MOESM1_ESM.docx (4.5 mb)
Supplementary Information

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Ulviye Acar Çevik
    • 1
    • 2
    Email author
  • Derya Osmaniye
    • 1
    • 2
  • Betül Kaya Çavuşoğlu
    • 1
    • 2
  • Begüm Nurpelin Sağlik
    • 1
    • 2
  • Serkan Levent
    • 1
    • 2
  • Sinem Ilgin
    • 3
  • Nafiz Öncü Can
    • 4
  • Yusuf Özkay
    • 1
    • 2
  • Zafer Asım Kaplancikli
    • 1
  1. 1.Faculty of Pharmacy, Department of Pharmaceutical ChemistryAnadolu UniversityEskişehirTurkey
  2. 2.Faculty of Pharmacy, Doping and Narcotic Compounds Analysis LaboratoryAnadolu UniversityEskişehirTurkey
  3. 3.Department of Pharmaceutical ToxicologyFaculty of Pharmacy, Anadolu UniversityEskişehirTurkey
  4. 4.Faculty of Pharmacy, Department of Analytical ChemistryAnadolu UniversityEskişehirTurkey

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