Synthesis and evaluation of anti-Giardia activity of oseltamivir analogs

Bioorg Med Chem Lett. 2025 Feb 1:116:130035. doi: 10.1016/j.bmcl.2024.130035. Epub 2024 Nov 25.

Abstract

We reported earlier that oseltamivir (Osm, Tamiflu®), an anti-viral agent, inhibits the attachment of trophozoites to intestinal epithelial cells and cyst production in culture. Osm also disassembles lipid rafts (LRs) and the biogenesis of extracellular vesicles (EVs) by Giardia. In the current study, we synthesized forty-one Osm analogs with the derivatization of oseltamivir phosphate. These compounds were tested on giardial growth, and cyst production. Of these, four analogs, i.e., compounds 3b, 2c, 11i, and 11d, were found to have superior activities against trophozoites and cysts compared to the parent oseltamivir. Investigation of the mechanism(s) of action of these agents are in progress and will be reported in due course.

Keywords: Anti-giardiasis; Cyst; Giardia; Oseltamivir; Trophozoite.

MeSH terms

  • Antiprotozoal Agents / chemical synthesis
  • Antiprotozoal Agents / chemistry
  • Antiprotozoal Agents / pharmacology
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • Dose-Response Relationship, Drug
  • Giardia lamblia / drug effects
  • Humans
  • Molecular Structure
  • Oseltamivir* / chemical synthesis
  • Oseltamivir* / chemistry
  • Oseltamivir* / pharmacology
  • Structure-Activity Relationship

Substances

  • Oseltamivir
  • Antiviral Agents
  • Antiprotozoal Agents