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Research on Chemical Intermediates

, Volume 45, Issue 5, pp 2827–2854 | Cite as

Anti-cancer, anti-oxidant and molecular docking studies of thiosemicarbazone indole-based derivatives

  • Zohreh Bakherad
  • Maliheh Safavi
  • Afshin Fassihi
  • Hojjat Sadeghi-Aliabadi
  • Mohammad Bakherad
  • Hossein Rastegar
  • Jahan B. Ghasemi
  • Saghi Sepehri
  • Lotfollah SaghaieEmail author
  • Mohammad MahdaviEmail author
Article
  • 49 Downloads

Abstract

Based on the structural elements of bioactive 3-substituted indoles, a new series of indole–thiosemicarbazone hybrid derivatives were designed, synthesized, and well-characterized using different spectral techniques. The intended scaffolds were screened for their in vitro anti-proliferative activities against breast cancer (MCF-7), lung cancer (A-549), and liver cancer (Hep-G2) cell lines, as well as their anti-oxidant properties. Cytotoxicity studies revealed that compound 6n was the most potent, at least threefold more potent than the commercially available reference drug etoposide, against A-549. In addition, morphological analysis by the acridine orange/ethidium bromide double staining test and flow cytometry analysis confirmed induction of apoptosis in the A-549 cells by compound 6n. In order to validate the experimental results, molecular studies were performed to achieve the possible binding interactions of the most potent compound (6n) and colchicine with tubulin as well as ANP with ATPase domain of topoisomerase IIα active sites. Moreover, the radical scavenging potential of the final derivatives was found to be excellent with the range of 0.015–0.630 µM, comparable to the standard ascorbic acid (0.655 µM).

Keywords

Indole Thiosemicarbazone Anti-oxidant Anti-cancer Apoptosis Flow cytometry 

Notes

Acknowledgements

This work was supported by Grants from Isfahan university of Medical Sciences and Tehran University of Medical Sciences.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interests.

Supplementary material

11164_2019_3765_MOESM1_ESM.docx (2.7 mb)
Supplementary material 1 (DOCX 2759 kb)

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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Zohreh Bakherad
    • 1
  • Maliheh Safavi
    • 2
  • Afshin Fassihi
    • 1
  • Hojjat Sadeghi-Aliabadi
    • 1
  • Mohammad Bakherad
    • 3
  • Hossein Rastegar
    • 4
  • Jahan B. Ghasemi
    • 5
  • Saghi Sepehri
    • 6
  • Lotfollah Saghaie
    • 1
    Email author
  • Mohammad Mahdavi
    • 7
    Email author
  1. 1.Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical SciencesIsfahan University of Medical SciencesIsfahanIran
  2. 2.Department of BiotechnologyIranian Research Organization for Science and TechnologyTehranIran
  3. 3.School of ChemistryShahrood University of TechnologyShahroodIran
  4. 4.Food and Drug Control Laboratories, Food and Drug Laboratory Research CenterMOE and METehranIran
  5. 5.Drug Design in Silico Lab, Chemistry Faculty, School of SciencesUniversity of TehranTeheranIran
  6. 6.Department of Medicinal Chemistry, School of PharmacyArdabil University of Medical SciencesArdabilIran
  7. 7.Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Research InstituteTehran University of Medical SciencesTehranIran

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