Design, synthesis, and biological activities of conformationally restricted analogs of primaquine with a 1,10-phenanthroline framework

Bioorg Med Chem Lett. 2008 Aug 15;18(16):4666-9. doi: 10.1016/j.bmcl.2008.07.013. Epub 2008 Jul 10.

Abstract

A series of primaquine analogs was prepared, according to a conformationally restricted conformation of primaquine. In vitro antiplasmodial activities were evaluated and showed that all compounds were active on different strains of Plasmodium falciparum. In particular compounds 5 and 15 possessing a methoxy group were more active than was primaquine. Furthermore, analog 5 displayed good in vitro gametocytocidal activity. In addition selectivity indexes were calculated in respect with cytotoxic activities on Vero cell lines.

MeSH terms

  • Animals
  • Antimalarials / pharmacology*
  • Chemistry, Pharmaceutical / methods*
  • Chlorocebus aethiops
  • Chloroquine / pharmacology
  • Drug Design
  • Inhibitory Concentration 50
  • Models, Chemical
  • Molecular Conformation
  • Phenanthrolines / chemical synthesis
  • Phenanthrolines / chemistry*
  • Plasmodium falciparum / drug effects
  • Primaquine / chemistry
  • Vero Cells

Substances

  • Antimalarials
  • Phenanthrolines
  • Chloroquine
  • Primaquine
  • 1,10-phenanthroline