Design, synthesis and biological evaluation of novel HIV-1 protease inhibitors with pentacyclic triterpenoids as P2-ligands

Bioorg Med Chem Lett. 2019 Feb 1;29(3):357-361. doi: 10.1016/j.bmcl.2018.12.040. Epub 2018 Dec 18.

Abstract

The design, synthesis and SAR study of a new series of HIV-1 protease inhibitors with pentacyclic triterpenoids as P2 ligands and phenylsulfonamide as P2' ligands were discussed. These compounds exhibited micromolar inhibitory potency, among which compound T1c displayed HIV-1 protease inhibition with IC50 values of 0.12 μM, which was 67 times the inhibitory activity of its raw material Ursolic acid (8.0 μM).

Keywords: HIV-1 protease inhibitors; P2 ligand; Pentacyclic triterpenoids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Design*
  • HIV Protease / metabolism*
  • HIV Protease Inhibitors / chemical synthesis
  • HIV Protease Inhibitors / chemistry
  • HIV Protease Inhibitors / pharmacology*
  • HIV-1 / drug effects
  • Humans
  • Ligands
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Pentacyclic Triterpenes / chemical synthesis
  • Pentacyclic Triterpenes / chemistry
  • Pentacyclic Triterpenes / pharmacology*
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*

Substances

  • Anti-HIV Agents
  • HIV Protease Inhibitors
  • Ligands
  • Pentacyclic Triterpenes
  • Sulfonamides
  • HIV Protease
  • p16 protease, Human immunodeficiency virus 1