Stereochemical insights into enantioselective antiplasmodial lignanamides from the twigs and leaves of Solanum erianthum

Phytochemistry. 2024 Aug:224:114163. doi: 10.1016/j.phytochem.2024.114163. Epub 2024 May 28.

Abstract

Stereochemical investigations on the twigs and leaves of Solanum erianthum afforded five pairs of lignanamide enantiomers and a previously undescribed phenolic amide (3). Particularly, two pairs of previously undescribed lignanamide racemates (1a/1b-2a/2b) represent the first case of natural products that feature an unreported 5/5-fused N/O-biheterocyclic core. Their structures, including the absolute configurations, were determined unambiguously by using spectroscopic analyses and electronic circular dichroism calculations. A speculative biogenetic pathway for 1-3 was proposed. Interestingly, these lignanamides exhibited enantioselective antiplasmodial activities against drug-sensitive Plasmodium falciparum 3D7 strain and chloroquine-resistant Plasmodium falciparum Dd2 strain, pointing out that chirality plays an important role in drug development.

Keywords: Antiplasmodial activity; Chiral resolution; Enantiomers; Lignanamides; Solanaceae; Solanum erianthum.

MeSH terms

  • Amides / chemistry
  • Amides / isolation & purification
  • Amides / pharmacology
  • Antimalarials* / chemistry
  • Antimalarials* / isolation & purification
  • Antimalarials* / pharmacology
  • Lignans / chemistry
  • Lignans / isolation & purification
  • Lignans / pharmacology
  • Molecular Structure
  • Parasitic Sensitivity Tests
  • Plant Leaves* / chemistry
  • Plasmodium falciparum* / drug effects
  • Solanum* / chemistry
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Antimalarials
  • Lignans
  • Amides