Novel Linezolid analogues with antiparasitic activity against Hymenolepis nana

Eleazar Alcántar-Zavala, Esteban Hernández-Guevara, Adrián Ochoa-Terán*, Julio Montes-Ávila, Edgar A. Estrada-Zavala, Alex J. Salazar-Medina, Efraín Alday, Alberto Cabrera, Gerardo Aguirre, Valentín Miranda-Soto, Carlos Velazquez, Sylvia P. Díaz-Camacho, José L. Medina-Franco

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

The stereoselective synthesis and anti- Hymenolepis nana activity of six Linezolid-type compounds, obtained by chemical modification of L-Alanine, are reported in this work. The synthetic strategy was to prepare diasteromeric N,N-dibenzylamino oxazolidinones 1 and 2, and coupling with 4-(4-bromophenyl)morpholine (3) to obtain N,N-dibenzylamino Linezolid analogues 4 and 5. A hydrogenolysis reaction over 4 and 5 resulted in amino-free Linezolid analogues 6 and 7, which were acetylated to reach diasteromeric Linezolid analogues 8 and 9. The six Linezolid analogues 4–9 show in vitro antiparasitic activity against Hymenolepis nana cestode, but not against several bacterial strains. Interestingly, compounds 6, 7 and 9 exhibit high potency, having shorter paralysis and death times after exposure (6–10 and 18–21 min, respectively), shorter than those found with antihelmintic compound Praziquantel (20 and 30 min) at 20 mg/mL. In addition, a cytocompatibility assay of 6–9 with human cells (ARPE-19 cells) demonstrate a non-cytotoxic effect at 0.4 mM. These results show the pharmacological potential of the newly reported Linezolid-type analogues as antiparasitic agents against Hymenolepis nana.

Original languageEnglish
Article number104359
JournalBioorganic Chemistry
Volume105
DOIs
StatePublished - Dec 2020

Bibliographical note

Publisher Copyright:
© 2020 Elsevier Inc.

Keywords

  • Antiparasitic activity
  • Linezolid analogues
  • Stereoselective synthesis

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