New salicylamide and sulfonamide derivatives of quinoxaline 1,4-di-N-oxide with antileishmanial and antimalarial activities

Bioorg Med Chem Lett. 2011 Aug 1;21(15):4498-502. doi: 10.1016/j.bmcl.2011.05.125. Epub 2011 Jun 12.

Abstract

Continuing with our efforts to identify new active compounds against malaria and leishmaniasis, 14 new 3-amino-1,4-di-N-oxide quinoxaline-2-carbonitrile derivatives were synthesized and evaluated for their in vitro antimalarial and antileishmanial activity against Plasmodium falciparum Colombian FCR-3 strain and Leishmania amazonensis strain MHOM/BR/76/LTB-012A. Further computational studies were carried out in order to analyze graphic SAR and ADME properties. The results obtained indicate that compounds with one halogenous group substituted in position 6 and 7 provide an efficient approach for further development of antimalarial and antileishmanial agents. In addition, interesting ADME properties were found.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimalarials / chemistry*
  • Antimalarials / pharmacokinetics
  • Antimalarials / toxicity
  • Leishmania mexicana / drug effects*
  • Macrophages / drug effects
  • Macrophages / immunology
  • Mice
  • Plasmodium falciparum / drug effects
  • Quinoxalines / chemistry*
  • Salicylamides / chemistry*
  • Salicylamides / pharmacokinetics
  • Salicylamides / toxicity
  • Structure-Activity Relationship
  • Sulfonamides / chemistry*
  • Sulfonamides / pharmacokinetics
  • Sulfonamides / toxicity
  • Trypanocidal Agents / chemistry*
  • Trypanocidal Agents / pharmacokinetics
  • Trypanocidal Agents / toxicity

Substances

  • Antimalarials
  • Quinoxalines
  • Salicylamides
  • Sulfonamides
  • Trypanocidal Agents
  • salicylamide