Synthesis and evaluation of 3-hydroxy-3-phenylpropanoate ester–AZT conjugates as potential dual-action HIV-1 Integrase and Reverse Transcriptase inhibitors

Bioorg Med Chem. 2015 Dec 15;23(24):7521-8. doi: 10.1016/j.bmc.2015.10.039.

Abstract

Novel 3-hydroxy-3-phenylpropanoate ester-azidothymidine (AZT) conjugates have been prepared using Baylis-Hillman methodology, and their potential as dual-action HIV-1 Integrase and Reverse Transcriptase inhibitors has been explored using enzyme inhibition and computer modelling techniques; their activity and HeLa cell toxicity have been compared with those of their cinnamate ester analogues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents
  • HIV Infections / drug therapy
  • HIV Infections / virology
  • HIV Integrase / metabolism
  • HIV Integrase Inhibitors / chemical synthesis
  • HIV Integrase Inhibitors / chemistry*
  • HIV Integrase Inhibitors / pharmacology*
  • HIV Reverse Transcriptase / antagonists & inhibitors
  • HIV Reverse Transcriptase / metabolism
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • HeLa Cells
  • Humans
  • Molecular Docking Simulation
  • Reverse Transcriptase Inhibitors / chemical synthesis
  • Reverse Transcriptase Inhibitors / chemistry*
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • Zidovudine / chemical synthesis
  • Zidovudine / chemistry*
  • Zidovudine / pharmacology*

Substances

  • Anti-HIV Agents
  • HIV Integrase Inhibitors
  • Reverse Transcriptase Inhibitors
  • Zidovudine
  • HIV Integrase
  • HIV Reverse Transcriptase
  • p31 integrase protein, Human immunodeficiency virus 1