Synthesis, antiplasmodial activity and mechanistic studies of pyrimidine-5-carbonitrile and quinoline hybrids

Eur J Med Chem. 2015 Aug 28:101:52-62. doi: 10.1016/j.ejmech.2015.06.024. Epub 2015 Jun 12.

Abstract

A series of hybrids comprising of 5-cyanopyrimidine and quinoline moiety were synthesized and tested for in vitro antiplasmodial activity against NF54 and Dd2 strains of Plasmodium falciparum. Hybrid bearing m-nitrophenyl substituent at C-4 of pyrimidine displayed the highest antiplasmodial activity [IC50 = 56 nM] against the CQ(R) (Dd2) strain, which is four-fold greater than CQ.

Keywords: 4-Aminoquinoline; Antiplasmodial agents; Cytotoxic activity; Heme binding; Hybrid antimalarials; Pyrimidine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimalarials / chemical synthesis*
  • Antimalarials / chemistry
  • Antimalarials / pharmacology*
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • Cell Line
  • DNA Viruses / drug effects
  • Dose-Response Relationship, Drug
  • Heme / chemistry
  • Humans
  • Mice
  • Models, Molecular
  • Molecular Structure
  • Nitriles / chemistry
  • Nitriles / pharmacology*
  • Parasitic Sensitivity Tests
  • Plasmodium falciparum / drug effects*
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*
  • Quinolines / chemistry
  • Quinolines / pharmacology*
  • RNA Viruses / drug effects
  • Structure-Activity Relationship

Substances

  • Antimalarials
  • Antiviral Agents
  • Nitriles
  • Pyrimidines
  • Quinolines
  • Heme
  • quinoline