Medicinal Chemistry Research

, Volume 26, Issue 5, pp 999–1009 | Cite as

Ethyl phosphoramidates of acyclovir: design, synthesis, molecular docking (HN Protein), and evaluation of antiviral and antioxidant activities

  • Subba Rao Devineni
  • Madhava Golla
  • Thaslim Basha Shaik
  • Janardhan Avilala
  • Madhu Sudhana Saddala
  • Narasimha Golla
  • Naga Raju ChamarthiEmail author
Original Research


Synthesis of a series of new ethyl phosphoramidates 9aj of acyclovir through phosphorylation of hydroxy group followed by substitution of numerous amines/amino acid esters 7aj was accomplished. The structures of newly synthesized compounds were elucidated by spectroscopic data such as IR, NMR (1H, 13C, and 31P) and mass spectrophotometery, and elemental analyses. The synthesized products were screened for their antiviral activity against Newcastle disease virus, antioxidant potency by α, α-diphenyl-β-picrylhydrazyl free radical scavenging and nitric oxide radical scavenging methods, and antioxidant capacity by Ferric reducing antioxidant power method. The compound bearing 1-hydroxy 2-butylamine, 9c and amino acid ester derivatives, bonded with leucine methyl ester 9h and tyrosine methyl ester 9j were found to be potent inhibiters of Newcastle disease virus than that of acyclovir drug. The compounds, 9c (IC50 value, 22.5 ± 1.00 μg/mL), 9i (IC50 value, 21.5 ± 1.00 μg/mL) and 9j (IC50 value, 19.0 ± 1.50 μg/mL) were exhibited promising antioxidant activity while other compounds displayed moderate to good antioxidant activity. Docking study using molecular docking environment into haemaglutinin–neuraminidase protein has been carried out to find the potential selectivity and binding orientation of these new compounds into protein binding site. Interestingly, all the title compounds except 9a and 9g docked well into HN protein with considerable binding affinities better than that of acyclovir drug.


Acyclovir Phosphoramidates Antiviral activity Antioxidant activity Molecular docking study Hemagglutinin neuraminidase protein 



The author (DSR) acknowledges University Grants Commission for providing Senior Research Fellowship under the program of Basic Scientific Research (BSR), and SKTB and GM are thankful to University Grants Commission for providing financial assistance. Also, we grateful to K. Naresh, Department of Biochemistry, S. V. University and Hyderabad Central University for contributing antioxidant activity and providing analytical data, respectively.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

44_2017_1819_MOESM1_ESM.doc (1.2 mb)
Supplementary Information


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Subba Rao Devineni
    • 1
  • Madhava Golla
    • 1
  • Thaslim Basha Shaik
    • 1
  • Janardhan Avilala
    • 2
  • Madhu Sudhana Saddala
    • 3
  • Narasimha Golla
    • 2
  • Naga Raju Chamarthi
    • 1
    Email author
  1. 1.Department of ChemistrySri Venkateswara UniversityTirupatiIndia
  2. 2.Department of VirologySri Venkateswara UniversityTirupatiIndia
  3. 3.Department of BioinformaticsSri Venkateswara UniversityTirupatiIndia

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