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Synthesis, anti-proliferative activity, theoretical and 1H NMR experimental studies of Morita–Baylis–Hillman adducts from isatin derivatives

  • Vinicius B. M. Brito
  • Gilmar F. Santos
  • Thiago D. S. Silva
  • Júlia L. C. Souza
  • Gardenia C. G. Militão
  • Felipe T. Martins
  • Fábio P. L. Silva
  • Boaz G. Oliveira
  • Edigenia C. C. Araújo
  • Mário L. A. A. Vasconcellos
  • Claudio G. Lima-JúniorEmail author
  • Edilson B. Alencar-FilhoEmail author
Original Article
  • 54 Downloads

Abstract

Quaternary or spirocyclic 3-substituted-3-hydroxy-2-oxindole is considered a privileged scaffold. In other words, it is a molecular core present on several compounds with a wide spectrum of biological activities. Among its precursors, activated ketones (isatin nucleus) can be used as interesting starting points to Morita–Baylis–Hillman adducts derivatives, a class of compounds with good cytotoxic potential. In this paper, we present the synthesis, anti-proliferative activity against lung cancer cell line and a theoretical conformational study of 21 of Morita–Baylis–Hillman adducts from isatin derivatives, by DFT quantum chemical calculations, followed by a SAR and QSAR analysis. Besides, an efficient synthetic protocol and good biological activity profile were highlighted interesting observations about 1H NMR experimental spectra, molecular modeling results and crystallographic data available.

Graphical abstract

Keywords

Synthesis of Morita–Baylis–Hillman adducts from isatin derivatives Anti-proliferative activity 1H NMR spectroscopy DFT calculations and QSAR modeling X-Ray crystallography 

Notes

Acknowledgements

The authors are grateful to the Foundation of Support to the Science and Technology of the State of Pernambuco—FACEPE, National Council for Scientific and Technological Development––CNPQ, Coordination of Improvement of Higher Level Personnel—CAPES, Federal University of San Francisco Valley—UNIVASF, for financial support, National High-performance Processing Center of Federal University of Ceará—CENAPAD-UFC for some computational facilities as Gaussian 09 W package, Laboratory of Chromatography and Mass Spectrometry (LaCEM), Institute of Chemistry, Federal University of Goiás (Prof. Dr. Boniek Gontijo Vaz) for mass spectrometry analyses.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

11030_2019_9950_MOESM1_ESM.docx (2.8 mb)
Supplementary material 1 (DOCX 2876 kb)

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Vinicius B. M. Brito
    • 1
  • Gilmar F. Santos
    • 2
  • Thiago D. S. Silva
    • 3
  • Júlia L. C. Souza
    • 3
  • Gardenia C. G. Militão
    • 3
  • Felipe T. Martins
    • 5
  • Fábio P. L. Silva
    • 2
  • Boaz G. Oliveira
    • 4
  • Edigenia C. C. Araújo
    • 1
  • Mário L. A. A. Vasconcellos
    • 2
  • Claudio G. Lima-Júnior
    • 2
    Email author
  • Edilson B. Alencar-Filho
    • 1
    Email author
  1. 1.Postgraduate Program of Biosciences (ex-Natural Resources of Semi-arid), Postgraduate Program of Health and Biological Sciences, Collegiate of Pharmaceutical SciencesFederal University of San Francisco Valley (UNIVASF)PetrolinaBrazil
  2. 2.LASOM-PB, Departament of ChemistryFederal University of Paraiba (UFPB)ParaibaBrazil
  3. 3.Department of Physiology and PharmacologyFederal University of Pernambuco (UFPE)RecifeBrazil
  4. 4.LQTAIM, Postgraduate Program of Pure and Applied ChemistryFederal University of West Bahia (UFOB)BahiaBrazil
  5. 5.Institute of ChemistryFederal University of Goias (UFG)GoiâniaBrazil

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