Synthesis and evaluation of substituted 4-arylimino-3-hydroxybutanoic acids as potential HIV-1 integrase inhibitors

Bioorg Med Chem Lett. 2018 Apr 1;28(6):1067-1070. doi: 10.1016/j.bmcl.2018.02.020. Epub 2018 Feb 12.

Abstract

A series of readily accessible 4-arylimino-3-hydroxybutanoic acids have been prepared and evaluated as potential HIV-1 Integrase inhibitors. None of the ligands exhibited significant toxicity against human embryonic kidney (HEK 293) cells, while five of them showed activity against HIV-1 integrase - the most active (6c) with an IC50 value of 3.5 μM. In silico docking studies indicate the capacity of ligand 6c to interact with several amino acid residues and the two Mg2+ cations in the HIV-1 integrase receptor cavity.

Keywords: 4-Arylimino-3-hydroxybutanoic acids; HIV-1 integrase inhibitors; Synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dose-Response Relationship, Drug
  • HEK293 Cells
  • HIV Integrase / metabolism*
  • HIV Integrase Inhibitors / chemical synthesis
  • HIV Integrase Inhibitors / chemistry
  • HIV Integrase Inhibitors / pharmacology*
  • Humans
  • Hydroxybutyrates / chemical synthesis
  • Hydroxybutyrates / chemistry
  • Hydroxybutyrates / pharmacology*
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • HIV Integrase Inhibitors
  • Hydroxybutyrates
  • HIV Integrase