Medicinal Chemistry Research

, Volume 27, Issue 5, pp 1419–1431 | Cite as

Synthesis, characterization, and bioactivity of new bisamidrazone derivatives as possible anticancer agents

  • Malath A. Al-Qtaitat
  • Mustafa M. El-Abadelah
  • Dima A. Sabbah
  • Sanaa Bardaweel
  • Kamal Sweidan
  • Salim S. Sabri
  • Mohammad S. Mubarak
Original Research
  • 45 Downloads

Abstract

A novel series of new di-(N-piperazin-1-yl)amidrazones and related congeners (3as) was synthesized by reaction of Nʹ,Nʺ-(biphenyl-4,4ʹ-diyl)-bis(2-oxopropanehydrazonoyl chloride) (2) with a selected set of secondary amines in basic media. Structures of the newly synthesized compounds were confirmed by elemental analysis and by various spectroscopic techniques such as 1H NMR, 13C NMR, 2D-NMR, and ESI-HRMS spectral data. Prepared compounds have been screened for antitumor activity against different cancer cell lines including breast cancer (MCF-7), colon cancer (Caco-2), and Leukemia (K562) cell lines using the tetrazolium dye 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assay. Although with varying degrees, a significant growth inhibitory and cytotoxic effect was observed on all three cancer cell lines. Compounds 3a, 3b, 3c, 3d, and 3m, showed significant growth inhibitory and cytotoxic effect against the aforementioned cancer cell lines. Glide docking studies against PI3Kα demonstrated that some structural analogues accommodate PI3Kα kinase domain and bind to Ser774, Ala775, Glu798, Lys802, Tyr836, Val851, Asn853, Thr856, Gln859, Ser919, and Asp933. Additionally, part of the backbones of prepared compounds fit the pharmacophoric features of PI3Kα active inhibitors.

Keywords

Biphenyl-4,4’-amidrazone Bis(2-oxopropanehydrazonoyl chloride) Breast cancer Colon cancer Leukemia Docking PI3Kα kinase 

Notes

Acknowledgements

Authors wish to thank the Deanship of Scientific Research at The University of Jordan for financial support.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

44_2018_2158_MOESM1_ESM.docx (466 kb)
Supplementary Information
44_2018_2158_MOESM2_ESM.docx (971 kb)
Supplementary Figure

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Malath A. Al-Qtaitat
    • 1
  • Mustafa M. El-Abadelah
    • 1
  • Dima A. Sabbah
    • 2
  • Sanaa Bardaweel
    • 3
  • Kamal Sweidan
    • 1
  • Salim S. Sabri
    • 1
  • Mohammad S. Mubarak
    • 1
  1. 1.Department of Chemistry, Faculty of ScienceThe University of JordanAmmanJordan
  2. 2.Department of Pharmacy, Faculty of PharmacyAl-Zaytoonah University of JordanAmmanJordan
  3. 3.Department of Pharmaceutical Sciences, Faculty of PharmacyThe University of JordanAmmanJordan

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