Chemoenzymatic synthesis of new derivatives of glycyrrhetinic acid with antiviral activity. Molecular docking study

Bioorg Chem. 2018 Aug:78:210-219. doi: 10.1016/j.bioorg.2018.03.018. Epub 2018 Mar 19.

Abstract

We present an efficient approach to the synthesis of a series of glycyrrhetinic acid derivatives. Six derivatives, five of them new compounds, were obtained through chemoenzymatic reactions in very good to excellent yield. In order to find the optimal reaction conditions, the influence of various parameters such as enzyme source, nucleophile:substrate ratio, enzyme:substrate ratio, solvent and temperature was studied. The excellent results obtained by lipase catalysis made the procedure very efficient considering their advantages such as mild reaction conditions and low environmental impact. Moreover, in order to explain the reactivity of glycyrrhetinic acid and the acetylated derivative to different nucleophiles in the enzymatic reactions, molecular docking studies were carried out. In addition, one of the synthesized compounds exhibited remarkable antiviral activity against TK + and TK- strains of Herpes simplex virus type 1 (HSV-1), sensitive and resistant to acyclovir (ACV) treatment.

Keywords: Antivirals; Glycyrrhetinic acid; Lipase-catalyzed; Molecular modeling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyclovir / pharmacology
  • Antiviral Agents / chemistry
  • Antiviral Agents / metabolism
  • Antiviral Agents / pharmacology*
  • Biocatalysis
  • Candida / enzymology
  • Carica / enzymology
  • Dose-Response Relationship, Drug
  • Eurotiales / enzymology
  • Glycyrrhetinic Acid / chemistry
  • Glycyrrhetinic Acid / metabolism
  • Glycyrrhetinic Acid / pharmacology*
  • Herpesvirus 1, Human / drug effects*
  • Lipase / metabolism*
  • Microbial Sensitivity Tests
  • Molecular Docking Simulation*
  • Molecular Structure
  • Rhizomucor / enzymology
  • Rhizopus / enzymology
  • Structure-Activity Relationship

Substances

  • Antiviral Agents
  • Lipozyme
  • Lipase
  • Glycyrrhetinic Acid
  • Acyclovir