Ionic derivatives of betulinic acid exhibit antiviral activity against herpes simplex virus type-2 (HSV-2), but not HIV-1 reverse transcriptase

Bioorg Med Chem Lett. 2015 Aug 15;25(16):3168-71. doi: 10.1016/j.bmcl.2015.05.099. Epub 2015 Jun 6.

Abstract

Betulinic acid (1) has been modified to ionic derivatives (2-5) to improve its water solubility and biological activities. The binding properties of these derivatives with respect to human serum albumin (HSA) was examined and found to be similar to current anti-HIV drugs. These compounds did not inhibit HIV reverse transcriptase, however, 1, 2 and 5 inhibited herpes simplex type 2 (HSV-2) replication at concentrations similar to those reported for acyclovir (IC50 ∼ 0.1-10 μM) and with minimal cellular cytotoxicity. IC50 values for antiviral activity against HSV-2 186 were 1.6, 0.6, 0.9, 7.2, and 0.9 μM for compounds 1-5, respectively.

Keywords: Betulinic acid; HIV-1 reverse transcriptase; Herpes simplex type 2 (HSV-2); Inhibitor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyclovir / pharmacology
  • Animals
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • Betulinic Acid
  • Chlorocebus aethiops
  • HIV Reverse Transcriptase / antagonists & inhibitors
  • HIV Reverse Transcriptase / metabolism
  • HIV-1 / enzymology
  • Herpesvirus 2, Human / physiology*
  • Humans
  • Pentacyclic Triterpenes
  • Triterpenes / chemistry*
  • Triterpenes / pharmacology
  • Vero Cells
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Pentacyclic Triterpenes
  • Triterpenes
  • reverse transcriptase, Human immunodeficiency virus 1
  • HIV Reverse Transcriptase
  • Acyclovir
  • Betulinic Acid