Synthesis, Anti-Influenza H1N1 and Anti-Dengue Activity of A-Ring Modified Oleanonic Acid Polyamine Derivatives

Molecules. 2022 Dec 2;27(23):8499. doi: 10.3390/molecules27238499.

Abstract

A series of sixteen A-ring modified (2,3-indolo-, 2-benzylidene) oleanonic acid derivatives, holding some cyclic amines, linear polyamines and benzylaminocarboxamides at C28, has been synthesized and screened for antiviral activity against influenza A/PuertoRico/8/34 (H1N1) and Dengue virus serotypes of DENV-1, -2, -3, -4. It was found that 28-homopiperazine 2 and 3-N-phthalyl 22 amides of oleanonic acid demonstrated high potency with selectivity index SI 27 (IC50 21 μM) and 42 (IC50 12 μM). Oleanonic acid aminoethylpiperazine amide 6 and C-azepano-erythrodiol 23 appeared to be the most effective compounds against DENV-1 (IC50's 67 and 107 μM) and -2 (IC50's 86 and 68 μM correspondingly) serotypes.

Keywords: Dengue virus; Ugi derivatives; antiviral activity; benzylidene; indole; influenza A (H1N1); oleanolic acid; polyamine; triterpenoids.

MeSH terms

  • Amides / therapeutic use
  • Antiviral Agents / therapeutic use
  • Humans
  • Influenza A Virus, H1N1 Subtype*
  • Influenza, Human* / drug therapy
  • Polyamines / pharmacology
  • Polyamines / therapeutic use
  • Triterpenes* / therapeutic use

Substances

  • oleanonic acid
  • Polyamines
  • Triterpenes
  • Antiviral Agents
  • Amides