Antimalarial and antitrypanosomal activity of a series of amide and sulfonamide derivatives of a 2,5-diaminobenzophenone

Bioorg Med Chem. 2009 Nov 15;17(22):7690-7. doi: 10.1016/j.bmc.2009.09.043. Epub 2009 Sep 25.

Abstract

Here, we describe a series of readily obtainable benzophenone derivatives with antimalarial and antitrypanosomal activity. The most active compounds display submicromolar activity against Plasmodium falciparum. Micromolar activity is obtained against Trypanosoma brucei. Main problem of the compounds is low selectivity. However, there are indications that separation of antimalarial and cytotoxic activity might by possible. In addition, some compounds inhibit human ABC transporter with nanomolar activity.

MeSH terms

  • Amides / chemical synthesis
  • Amides / chemistry*
  • Amides / pharmacology*
  • Antimalarials / chemical synthesis*
  • Antimalarials / chemistry
  • Antimalarials / pharmacology
  • Benzophenones / chemical synthesis
  • Benzophenones / chemistry*
  • Benzophenones / pharmacology
  • Inhibitory Concentration 50
  • Malaria / drug therapy
  • Malaria / parasitology
  • Parasitic Sensitivity Tests
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / growth & development
  • Plasmodium falciparum / metabolism
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*
  • Trypanosoma brucei brucei / drug effects*
  • Trypanosoma brucei brucei / growth & development
  • Trypanosoma brucei brucei / metabolism

Substances

  • 2,5-diaminobenzophenone
  • Amides
  • Antimalarials
  • Benzophenones
  • Sulfonamides