Substituted 1,3-dioxoisoindoline-4-aminoquinolines coupled via amide linkers: Synthesis, antiplasmodial and cytotoxic evaluation

Bioorg Chem. 2019 Jul:88:102912. doi: 10.1016/j.bioorg.2019.04.006. Epub 2019 Apr 11.

Abstract

Synthesis of C-5-substituted 1,3-dioxoisoindoline-4-aminoquinolines having amide group as a spacer was developed with an intent to evaluate their antiplasmodial activities. The synthesized dioxoisoindoline-aminoquinolines tethered with β-alanine as a spacer and secondary amine as substituent displayed good anti-plasmodial activities. Compound 7j, with an optimum combination of β-alanine and an ethyl chain length as linker along with diethylamine as the secondary amine counterpart at dioxoisoindoline proved to be most potent and non-cytotoxic with IC50 of 0.097 µM against W2 strain of P. falciparum and a selective index of >2000.

Keywords: 1,3-Dioxoisoindoline-4-aminoquinolines; Antiplasmodial; Cytotoxicity; Microwave; Selectivity index.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoquinolines / chemical synthesis
  • Aminoquinolines / pharmacology*
  • Aminoquinolines / toxicity
  • Animals
  • Antimalarials / chemical synthesis
  • Antimalarials / pharmacology*
  • Antimalarials / toxicity
  • Cell Survival / drug effects
  • Chlorocebus aethiops
  • Molecular Structure
  • Parasitic Sensitivity Tests
  • Phthalimides / chemical synthesis
  • Phthalimides / pharmacology*
  • Phthalimides / toxicity
  • Plasmodium falciparum / drug effects
  • Structure-Activity Relationship
  • Vero Cells

Substances

  • Aminoquinolines
  • Antimalarials
  • Phthalimides