Synthesis of 2-(N-cyclicamino)quinoline combined with methyl (E)-3-(2/3/4-aminophenyl)acrylates as potential antiparasitic agents

Arch Pharm (Weinheim). 2021 Jul;354(7):e2000331. doi: 10.1002/ardp.202000331. Epub 2021 Mar 12.

Abstract

A rationally designed series of 2-(N-cyclicamino)quinolines coupled with methyl (E)-3-(2/3/4-aminophenyl)acrylates was synthesized and subjected to in vitro screening bioassays for potential antiplasmodial and antitrypanosomal activities against a chloroquine-sensitive (3D7) strain of Plasmodium falciparum and nagana Trypanosoma brucei brucei 427, respectively. Substituent effects on activity were evaluated; meta-acrylate 24 and the ortho-acrylate 29 exhibited the highest antiplasmodial (IC50 = 1.4 µM) and antitrypanosomal (IC50 = 10.4 µM) activities, respectively. The activity against HeLa cells showed that the synthesized analogs are not cytotoxic at the maximum tested concentration. The ADME (absorption, distribution, metabolism, and excretion) drug-like properties of the synthesized compounds were predicted through the SwissADME software.

Keywords: 2-(N-cyclicamino)quinolines; ADME; aminophenylacrylates; antiplasmodial; antitrypanosomal.

MeSH terms

  • Acrylates / chemical synthesis
  • Acrylates / chemistry
  • Acrylates / pharmacology*
  • Antimalarials / chemical synthesis
  • Antimalarials / chemistry
  • Antimalarials / pharmacology*
  • HeLa Cells
  • Humans
  • Inhibitory Concentration 50
  • Plasmodium falciparum / drug effects
  • Quinolines / chemical synthesis
  • Quinolines / chemistry
  • Quinolines / pharmacology*
  • Structure-Activity Relationship
  • Trypanocidal Agents / chemical synthesis
  • Trypanocidal Agents / chemistry
  • Trypanocidal Agents / pharmacology*
  • Trypanosoma brucei brucei / drug effects

Substances

  • Acrylates
  • Antimalarials
  • Quinolines
  • Trypanocidal Agents