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Syntheses and in silico pharmacokinetic predictions of glycosylhydrazinyl-pyrazolo[1,5-c]pyrimidines and pyrazolo[1,5-c]triazolo[4,3-a]pyrimidines as anti-proliferative agents

  • Kamal F. M. Atta
  • Omaima O. M. Farahat
  • Tareq Q. Al-Shargabi
  • Mohamed G. Marei
  • Tamer M. Ibrahim
  • Adnan A. BekhitEmail author
  • El Sayed H. El AshryEmail author
Original Research
  • 104 Downloads

Abstract

New glycosylhydrazinyl-pyrazolo[1,5-c]pyrimidines were synthesized by the reaction of respective 5-aryl-7-hydrazino-2-phenylpyrazolo[1,5-c]pyrimidines (1a-d) with glucose, galactose, and xylose in ethanol. Their glycopyranosyl structures were reasoned to be in chair conformations and each have hydrazine moiety in the β-configuration. Also, pyrazolo[1,5-c]triazolo[4,3-a]pyrimidines derivatives were synthesized by the reaction of 1a-d with benzoic acid in the presence of phosphorousoxy chloride or by the reaction with benzaldehyde derivatives followed by cyclization in the presence of bromine. All structures of the compounds were confirmed from their IR, 1H, 13C, DPET-135°, 1H-1H COSY, 1H-13C HMQC, 13C-1H HMBC spectra and microanalysis. The synthesized compounds showed inhibition of proliferation of MCF-7 human breast cancer cells with IC50 values ranging from 0.56 to 8.86 µg/ml. Some of the most active compounds showed acceptable predicted pharmacokinetics and drug-likeness properties.

Keywords

Glycosylhydrazine yrazolo[1,5-c]triazolo[4,3-a]pyrimidines 5-aryl-2-phenyl-7-(2-benzylidenehydrazinyl)pyrazolo[1,5-c]pyrimidines Cytotoxicity 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

44_2018_2277_MOESM1_ESM.pdf (2.7 mb)
Supplementary Information

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

Authors and Affiliations

  • Kamal F. M. Atta
    • 1
  • Omaima O. M. Farahat
    • 1
  • Tareq Q. Al-Shargabi
    • 2
  • Mohamed G. Marei
    • 1
  • Tamer M. Ibrahim
    • 3
  • Adnan A. Bekhit
    • 4
    • 5
    Email author
  • El Sayed H. El Ashry
    • 1
    Email author
  1. 1.Chemistry Department, Faculty of ScienceAlexandria UniversityAlexandriaEgypt
  2. 2.The Ministry of EducationTaizYemen
  3. 3.Pharmaceutical Chemistry Department, Faculty of PharmacyKafrelsheikh UniversityKafr El-SheikhEgypt
  4. 4.Pharmaceutical Chemistry Department, Faculty of PharmacyAlexandria UniversityAlexandriaEgypt
  5. 5.Pharmacy Program, Allied Health Department, College of Health SciencesUniversity of BahrainZallaqBahrain

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