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Synthesis and biological evaluation of phenyl-amino-pyrimidine and indole/oxindole conjugates as potential BCR-ABL inhibitors

  • Abdul Rahim
  • Riyaz Syed
  • Y. Poornachandra
  • M. Shaheer Malik
  • Ch. Venkata Ramana Reddy
  • Mallika Alvala
  • Kiran Boppana
  • B. Sridhar
  • Ramars Amanchy
  • Ahmed KamalEmail author
Original Research
  • 37 Downloads

Abstract

Indole/isatin conjugated phenyl-amino-pyrimidine derivatives have been synthesized, characterized and evaluated in vitro for their potential as BCR-ABL inhibitors. Among the series, all derivatives (7a7o) were found to be more cytotoxic than standard Imatinib against K-562 cell line. Compound 7l was the most active in the series with almost two folds more potency than imitanib (IC50 0.65 μM). In vitro enzymatic studies with recombinant ABL kinase enzyme exhibited promising inhibition in the range of 30–71 µM for most of these novel conjugates. In addition, modelling and other computational studies have been carried out to draw insight into the BCR-ABL protein interactions with the target molecules and drug like properties of the conjugates, respectively.

Synthesis and biological evaluation of phenyl-amino-pyrimidine and indole/oxindole conjugates as potential BCR-ABL inhibitors.

Keywords

Phenyl-amino-pyrimidine Indole Oxindole Bcr-Abl inhibitors Chronic myeloid leukemia 

Notes

Acknowledgements

The author AR thanks CSIR and UGC, New Delhi for the award of fellowships. The author RS thanks CSIR-HRDG for the award of CSIR-SRAship (13(8906-A)/2017-pool).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

44_2019_2318_MOESM1_ESM.docx (4.3 mb)
Supplementary Information.

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Copyright information

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

Authors and Affiliations

  • Abdul Rahim
    • 1
    • 2
  • Riyaz Syed
    • 1
    • 3
  • Y. Poornachandra
    • 4
  • M. Shaheer Malik
    • 5
  • Ch. Venkata Ramana Reddy
    • 3
  • Mallika Alvala
    • 6
  • Kiran Boppana
    • 7
  • B. Sridhar
    • 8
  • Ramars Amanchy
    • 4
  • Ahmed Kamal
    • 1
    • 6
    • 9
    Email author
  1. 1.Medicinal Chemistry and Biotechnology DivisionCSIR-Indian Institute of Chemical Technology (IICT)HyderabadIndia
  2. 2.Academy of Scientific and Innovative ResearchNew DelhiIndia
  3. 3.Department of ChemistryJ.N.T. UniversityKukatpally, HyderabadIndia
  4. 4.Division of Applied BiologyCSIR-Indian Institute of Chemical TechnologyTarnaka, HyderabadIndia
  5. 5.Central Research Laboratory and Department of Chemistry, Faculty of Applied SciencesUmm Al-Qura UniversityMakkahSaudi Arabia
  6. 6.Department of Medicinal ChemistryNational Institute of pharmaceutical Education and Research (NIPER)Balanagar, HyderabadIndia
  7. 7.GVK Bio Sciences Pvt. Ltd.HyderabadIndia
  8. 8.X-ray Crystallography DivisionCSIR-Indian Institute of Chemical TechnologyHyderabadIndia
  9. 9.School of Pharmaceutical Education and Research, Jamia HamdardNew DelhiIndia

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