Structure-activity relationships amongst 4-position quinoline methanol antimalarials that inhibit the growth of drug sensitive and resistant strains of Plasmodium falciparum

Bioorg Med Chem Lett. 2010 Feb 15;20(4):1347-51. doi: 10.1016/j.bmcl.2010.01.001. Epub 2010 Jan 7.

Abstract

Utilizing mefloquine as a scaffold, a next generation quinoline methanol (NGQM) library was constructed to identify early lead compounds that possess biological properties consistent with the target product profile for malaria chemoprophylaxis while reducing permeability across the blood-brain barrier. The library of 200 analogs resulted in compounds that inhibit the growth of drug sensitive and resistant strains of Plasmodium falciparum. Herein we report selected chemotypes and the emerging structure-activity relationship for this library of quinoline methanols.

Publication types

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

MeSH terms

  • Animals
  • Antimalarials / chemical synthesis*
  • Antimalarials / chemistry
  • Antimalarials / pharmacology
  • Drug Resistance, Fungal
  • Inhibitory Concentration 50
  • Mice
  • Molecular Structure
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / growth & development
  • Quinolines / chemical synthesis*
  • Quinolines / chemistry
  • Quinolines / pharmacology
  • Small Molecule Libraries / chemistry*
  • Small Molecule Libraries / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antimalarials
  • Quinolines
  • Small Molecule Libraries