Dispirotripiperazine-core compounds, their biological activity with a focus on broad antiviral property, and perspectives in drug design (mini-review)

Eur J Med Chem. 2021 Feb 5:211:113014. doi: 10.1016/j.ejmech.2020.113014. Epub 2020 Nov 12.

Abstract

Viruses are obligate intracellular parasites and have evolved to enter the host cell. To gain access they come into contact with the host cell through an initial adhesion, and some viruses from different genus may use heparan sulfate proteoglycans for it. The successful inhibition of this early event of the infection by synthetic molecules has always been an attractive target for medicinal chemists. Numerous reports have yielded insights into the function of compounds based on the dispirotripiperazine scaffold. Analysis suggests that this is a structural requirement for inhibiting the interactions between viruses and cell-surface heparan sulfate proteoglycans, thus preventing virus entry and replication. This review summarizes our current knowledge about the early history of development, synthesis, structure-activity relationships and antiviral evaluation of dispirotripiperazine-based compounds and where they are going in the future.

Keywords: Anticancer; Antivirals; DSTP27; Dispirotripiperazine; Heparan sulfate glycosaminoglycans; PDSTP; Virus attachment; Virus entry.

Publication types

  • Review

MeSH terms

  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Drug Design*
  • Heparan Sulfate Proteoglycans / antagonists & inhibitors
  • Heparan Sulfate Proteoglycans / metabolism
  • Molecular Structure
  • Piperazines / chemistry
  • Piperazines / pharmacology*
  • Spiro Compounds / chemistry
  • Spiro Compounds / pharmacology*
  • Viruses / drug effects*
  • Viruses / metabolism

Substances

  • Antiviral Agents
  • Heparan Sulfate Proteoglycans
  • Piperazines
  • Spiro Compounds