Synthesis and in vitro evaluation of leishmanicidal and trypanocidal activities of N-quinolin-8-yl-arylsulfonamides

Bioorg Med Chem. 2007 Dec 15;15(24):7553-60. doi: 10.1016/j.bmc.2007.09.007. Epub 2007 Sep 12.

Abstract

In the present paper 12 N-quinolin-8-yl-arylsulfonamides synthesized by coupling 8-aminoquinolines with various arylsulfonylchlorides were assayed in vitro against Leishmania amazonensis, Leishmania chagasi and Trypanosoma cruzi strains. This series of new compounds were found to be selective for Leishmania spp. promastigote and amastigote forms. The most active compound was the N-(8-quinolyl)-3,5-difluoro-benzenesulfonamide 10 with an IC(50) against L. amazonensis and L. chagasi of 2.12 and 0.45 microM, respectively. The less cytotoxic biphenyl derivative 7 was very effective against intracellular L. amazonensis with a reduction of macrophage cell infection of 82.1% at 25 microM. In addition, a copper complex 17 of an inactive ligand was readily synthesized and showed high leishmanicidal and trypanocidal activity against both extra and intracellular forms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiprotozoal Agents / chemical synthesis
  • Antiprotozoal Agents / chemistry
  • Antiprotozoal Agents / pharmacology
  • Copper / chemistry
  • Inhibitory Concentration 50
  • Leishmania / drug effects*
  • Molecular Structure
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology
  • Parasitic Sensitivity Tests
  • Quinolines* / chemical synthesis
  • Quinolines* / chemistry
  • Quinolines* / pharmacology
  • Sulfonamides* / chemical synthesis
  • Sulfonamides* / chemistry
  • Sulfonamides* / pharmacology
  • Trypanocidal Agents / chemical synthesis*
  • Trypanocidal Agents / chemistry
  • Trypanocidal Agents / pharmacology
  • Trypanosoma cruzi / drug effects*
  • Zinc / chemistry

Substances

  • Antiprotozoal Agents
  • N-(8-quinolyl)-3,5-difluoro-benzenesulfonamide
  • Organometallic Compounds
  • Quinolines
  • Sulfonamides
  • Trypanocidal Agents
  • Copper
  • Zinc