Design, synthesis and anti-P. falciparum activity of pyrazolopyridine-sulfonamide derivatives

Bioorg Med Chem. 2016 Sep 15;24(18):4492-4498. doi: 10.1016/j.bmc.2016.07.049. Epub 2016 Jul 25.

Abstract

Ten 1-phenyl-1H-pyrazolo[3,4-b]pyridine derivatives connected by a linker group to benzenesulfonamide moieties with different substituents in the 4-position were synthesized and assayed against Plasmodium falciparum. These ten compounds exhibited activity in vitro against the chloroquine-resistant clone W2 with IC50 values ranging from 3.46 to 9.30μM. The most active derivatives with substituent R2=Cl or CH3 at the benzenesulfonamide moiety exhibited the lowest IC50. Compounds with an R1=CO2Et substituent at the 5-position of the 1H-pyrazolo[3,4-b]pyridine ring presented lower activity than those with a CN substituent. The 1H-pyrazolo[3,4-b]pyridine system appears to be promising for further studies as an antimalarial for overcoming the burden of resistance in P. falciparum.

Keywords: Malaria; Plasmodium falciparum; Pyrazolopyridine; Sulfonamide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimalarials / chemical synthesis*
  • Antimalarials / chemistry
  • Antimalarials / pharmacology*
  • Drug Design
  • Inhibitory Concentration 50
  • Plasmodium falciparum / drug effects*
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Pyridines / chemistry
  • Pyridines / pharmacology*
  • Spectrum Analysis / methods
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*

Substances

  • Antimalarials
  • Pyrazoles
  • Pyridines
  • Sulfonamides
  • pyrazolopyridine