Amalgamating Isatin/Indole/Nitroimidazole with 7-chloroquinolines via azide-alkyne cycloaddition: Synthesis, anti-plasmodial, and cytotoxic evaluation

Chem Biol Drug Des. 2020 Dec;96(6):1355-1361. doi: 10.1111/cbdd.13738. Epub 2020 Jun 25.

Abstract

The present paper describes the synthesis, anti-plasmodial, and cytotoxic evaluation of 7-chloroquinoline-based conjugates with isatins/indoles/ nitroimidazoles, obtained via Cu-promoted 1,3-dipolar cycloadditions. On contemplating SAR of the synthesized series, the inclusion of indole and nitroimidazole-core improved the anti-plasmodial activities while the isatin seemed to have a lesser effect. The conjugate with a nitroimidazole-core and hexyl chain length as a spacer between the two pharmacophores was found to be most potent among the synthesized series and displayed an IC50 of 0.12 µM and a selectivity index of 1748.

Keywords: 7-chloroquinoline-based conjugates; anti-plasmodial activity; azide-alkyne cycloaddition; cytotoxicity.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / chemistry
  • Antimalarials / chemical synthesis
  • Antimalarials / chemistry*
  • Antimalarials / pharmacology*
  • Azides / chemistry
  • Cycloaddition Reaction
  • Drug Screening Assays, Antitumor
  • Humans
  • Indoles / chemistry*
  • Isatin / chemistry*
  • Nitroimidazoles / chemistry*
  • Quinolones / chemistry*
  • Quinolones / pharmacology
  • Structure-Activity Relationship

Substances

  • Alkynes
  • Antimalarials
  • Azides
  • Indoles
  • Nitroimidazoles
  • Quinolones
  • Isatin