Synthesis of substituted aryloxy alkyl and aryloxy aryl alkyl imidazoles as antileishmanial agents

Bioorg Med Chem Lett. 2010 Jan 1;20(1):291-3. doi: 10.1016/j.bmcl.2009.10.117. Epub 2009 Oct 30.

Abstract

A series of aryloxy alkyl/aryl alkyl imidazoles were synthesized and evaluated in vitro as antileishmanials against Leishmania donovani. All the 19 compounds exhibited 94-100% inhibition at 10microg/mL against promastigotes and 12 compounds exhibited high inhibition with an IC(50) in the range of 0.47-4.85microg/mL against amastigotes. Promising compounds were tested further in vivo. Among all, compounds 4 and 23 with 4-CF(3) aryloxy moiety exhibited medium in vivo inhibition of 58-60%, thus providing new structural lead for antileishmanials.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Protozoan / metabolism
  • Antigens, Surface / metabolism
  • Antiprotozoal Agents / chemical synthesis*
  • Antiprotozoal Agents / chemistry
  • Antiprotozoal Agents / pharmacology
  • Cyclohexanes / chemistry
  • Imidazoles / chemical synthesis*
  • Imidazoles / chemistry
  • Imidazoles / pharmacology
  • Leishmania donovani / drug effects
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / metabolism
  • Neuraminidase / antagonists & inhibitors
  • Neuraminidase / metabolism
  • Protozoan Proteins / antagonists & inhibitors
  • Protozoan Proteins / metabolism
  • Structure-Activity Relationship

Substances

  • Antigens, Protozoan
  • Antigens, Surface
  • Antiprotozoal Agents
  • Cyclohexanes
  • Imidazoles
  • Membrane Proteins
  • Protozoan Proteins
  • surface antigen P2, Leishmania
  • Cyclohexane
  • amastigote surface protein-1
  • Neuraminidase