New pentasubstituted pyrrole hybrid atorvastatin-quinoline derivatives with antiplasmodial activity

Bioorg Med Chem Lett. 2016 Apr 15;26(8):1881-4. doi: 10.1016/j.bmcl.2016.03.027. Epub 2016 Mar 9.

Abstract

Cerebral malaria is caused by Plasmodium falciparum. Atorvastatin (AVA) is a pentasubstituted pyrrole, which has been tested as an adjuvant in the treatment of cerebral malaria. Herein, a new class of hybrids of AVA and aminoquinolines (primaquine and chloroquine derivatives) has been synthesized. The quinolinic moiety was connected to the pentasubstituted pyrrole from AVA by a linker group (CH2)n=2-4 units. The activity of the compounds increased with the size of the carbons chain. Compound with n=4 and 7-chloroquinolinyl has displayed better activity (IC50=0.40 μM) than chloroquine. The primaquine derivative showed IC50=1.41 μM, being less toxic and more active than primaquine.

Keywords: Atorvastatin; Chloroquine; Malaria; Pentasubstituted pyrrole; Primaquine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimalarials / chemical synthesis
  • Antimalarials / chemistry*
  • Antimalarials / pharmacology*
  • Atorvastatin / chemistry
  • Atorvastatin / pharmacology*
  • Dose-Response Relationship, Drug
  • Molecular Structure
  • Parasitic Sensitivity Tests
  • Plasmodium falciparum / drug effects*
  • Pyrroles / chemistry
  • Pyrroles / pharmacology*
  • Quinolines / chemistry
  • Quinolines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antimalarials
  • Pyrroles
  • Quinolines
  • Atorvastatin
  • quinoline