Benzoxaborole antimalarial agents. Part 2: Discovery of fluoro-substituted 7-(2-carboxyethyl)-1,3-dihydro-1-hydroxy-2,1-benzoxaboroles

Bioorg Med Chem Lett. 2012 Feb 1;22(3):1299-307. doi: 10.1016/j.bmcl.2011.12.096. Epub 2011 Dec 28.

Abstract

A series of new boron-containing benzoxaborole compounds was designed and synthesized for a continuing structure-activity relationship (SAR) investigation to assess the antimalarial activity changes derived from side-chain structural variation, substituent modification on the benzene ring and removal of boron from five-membered oxaborole ring. This SAR study demonstrated that boron is required for the antimalarial activity, and discovered that three fluoro-substituted 7-(2-carboxyethyl)-1,3-dihydro-1-hydroxy-2,1-benzoxaboroles (9, 14 and 20) have excellent potencies (IC(50) 0.026-0.209 μM) against Plasmodium falciparum.

MeSH terms

  • Antimalarials / chemical synthesis*
  • Antimalarials / chemistry
  • Antimalarials / pharmacology*
  • Antimalarials / toxicity
  • Boron Compounds / chemical synthesis*
  • Boron Compounds / chemistry
  • Boron Compounds / pharmacology*
  • Boron Compounds / toxicity
  • Bridged Bicyclo Compounds, Heterocyclic / chemical synthesis*
  • Bridged Bicyclo Compounds, Heterocyclic / chemistry
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
  • Bridged Bicyclo Compounds, Heterocyclic / toxicity
  • Cell Survival / drug effects
  • Fluorine / chemistry*
  • HeLa Cells
  • Humans
  • Inhibitory Concentration 50
  • Jurkat Cells
  • Molecular Structure
  • Plasmodium falciparum / drug effects*
  • Structure-Activity Relationship

Substances

  • Antimalarials
  • Boron Compounds
  • Bridged Bicyclo Compounds, Heterocyclic
  • Fluorine
  • tavaborole