Medicinal Chemistry Research

, Volume 23, Issue 5, pp 2242–2251 | Cite as

Phosphorylated ganciclovir derivatives: design, synthesis and in vitro and in vivo immunomodulatory activity

  • Kuruva Chandra Sekhar
  • Devineni Subba Rao
  • Kalla Chandra Mouli
  • Tartte Vijaya
  • Chamarthi Naga Raju
Original Research
First Online:
Received:
Accepted:

Abstract

Synthesis of a series of novel phosphorylated ganciclovir derivatives with bioactive amines/aminoacid esters as substituents was accomplished. These compounds were structurally characterized by IR, NMR (1H, 13C, 31P), mass spectra and CHN analysis. The compounds (5a–m) have been evaluated for its in vitro and in vivo immunomodulatory activities. The amino acid ester-substituted ganciclovir derivatives, especially the 5g and 5i, increased the intracellular killing activity of the stimulated neutrophils. The in vivo experiment results show that the administration of compounds 5g and 5i (8 mg/kg body weight) to diet-induced immune impaired obese rats ameliorated the significant increase in immune cell counts (lymphocytes, neutrophils and monocytes). In addition, TNF-α, IL-6 and IL-1 secretions were considerably restored to normal by the compounds 5g and 5i with regulation in the release of C-reactive protein suggesting their potentiating effect on immune system dysfunction. These in vitro and in vivo results suggest that the phosphorylated ganciclovir derivatives 5g and 5i are strong immunomodulators.

Keywords

Phosphorylated ganciclovir derivatives In vivo immunomodulatory activity In vitro nitroblue tetrazolium test Immune cell counts Immune modulating biofactors 
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Notes

Acknowledgments

The authors express their grateful thanks to BRNS (DAE) research project (2012/37C/21/BRNS/785), Mumbai, India for providing financial assistance through the project.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Kuruva Chandra Sekhar
    • 1
  • Devineni Subba Rao
    • 1
  • Kalla Chandra Mouli
    • 2
  • Tartte Vijaya
    • 3
  • Chamarthi Naga Raju
    • 1
  1. 1.Department of ChemistrySri Venkateswara UniversityTirupatiIndia
  2. 2.Department of BiotechnologySri Venkateswara UniversityTirupatiIndia
  3. 3.Department of BotanySri Venkateswara UniversityTirupatiIndia

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