Synthesis and anti-HIV activity of L-2',3'-Dideoxy-4'-selenonucleosides (L-4'-Se-ddNs)

Arch Pharm Res. 2019 Sep;42(9):780-789. doi: 10.1007/s12272-019-01157-6. Epub 2019 Apr 30.

Abstract

Based on the potent anti-HIV activity of L-2',3'-dideoxycytidine (L-ddC), L-2',3'-dideoxy-4'-selenonucleosides (L-4'-Se-ddNs) have been synthesized from natural chiral template, L-glutamic acid, using Pummerer-type condensation as a key step. All synthesized compounds were assayed for anti-HIV-1 activity, but none of them did show any significant antiviral activity up to 100 μM, probably due to conformational differences between L-ddC and L-4'-Se-ddC, induced by the bulky selenium atom, which might play an important role in phosphorylation by cellular kinase.

Keywords: Antiviral; L-2′,3′-Dideoxy-4′-selenonucleosides; L-4′-Se-ddC; L-Nucleoside; Pummerer-type condensation.

MeSH terms

  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • Dideoxynucleosides / chemical synthesis
  • Dideoxynucleosides / chemistry
  • Dideoxynucleosides / pharmacology*
  • Dose-Response Relationship, Drug
  • HIV / drug effects*
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Selenium Compounds / chemistry
  • Selenium Compounds / pharmacology*
  • Structure-Activity Relationship

Substances

  • Anti-HIV Agents
  • Dideoxynucleosides
  • Selenium Compounds