Design and synthesis of chalcone derivatives as inhibitors of the ferredoxin - ferredoxin-NADP+ reductase interaction of Plasmodium falciparum: pursuing new antimalarial agents

Molecules. 2014 Dec 19;19(12):21473-88. doi: 10.3390/molecules191221473.

Abstract

Some chalcones have been designed and synthesized using Claisen-Schmidt reactions as inhibitors of the ferredoxin and ferredoxin-NADP+ reductase interaction to pursue a new selective antimalaria agent. The synthesized compounds exhibited inhibition interactions between PfFd-PfFNR in the range of 10.94%-50%. The three strongest inhibition activities were shown by (E)-1-(4-aminophenyl)-3-(4-methoxyphenyl)prop-2-en-1-one (50%), (E)-1-(4-aminophenyl)-3-(2,4-dimethoxyphenyl)prop-2-en-1-one (38.16%), and (E)-1-(4-aminophenyl)-3-(2,3-dimethoxyphenyl)prop-2-en-1-one (31.58%). From the docking experiments we established that the amino group of the methoxyamino chlacone derivatives plays an important role in the inhibition activity by electrostatic interaction through salt bridges and that it forms more stable and better affinity complexes with FNR than with Fd.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimalarials / chemical synthesis*
  • Binding Sites
  • Chalcone / analogs & derivatives*
  • Chalcone / chemical synthesis*
  • Drug Design
  • Ferredoxin-NADP Reductase / antagonists & inhibitors*
  • Ferredoxin-NADP Reductase / chemistry
  • Ferredoxins / antagonists & inhibitors*
  • Ferredoxins / chemistry
  • Molecular Docking Simulation
  • Plant Proteins / chemistry
  • Plasmodium falciparum / drug effects
  • Plasmodium falciparum / enzymology
  • Protein Structure, Secondary
  • Protozoan Proteins / antagonists & inhibitors*
  • Protozoan Proteins / chemistry

Substances

  • Antimalarials
  • Ferredoxins
  • Plant Proteins
  • Protozoan Proteins
  • Chalcone
  • Ferredoxin-NADP Reductase