Comparison of the antiplasmodial and falcipain-2 inhibitory activity of beta-amino alcohol thiolactone-chalcone and isatin-chalcone hybrids

Bioorg Med Chem Lett. 2010 Apr 1;20(7):2234-7. doi: 10.1016/j.bmcl.2010.02.017. Epub 2010 Feb 10.

Abstract

The synthesis and biological evaluation of two novel series of natural-product-like hybrids based on the chalcone, thiolactone and isatin scaffolds is herein described. Results for a 36-member beta-amino alcohol triazole library showed that the thiolactone-chalcones, with IC(50)s ranging from 0.68 to 6.08 microM, were more active against W2 strain Plasmodium falciparum than the isatin-chalcones with IC(50)s of 14.9 microM or less. Also of interest is falcipain-2 inhibitory activity displayed by the latter, whereas the thiolactone-chalcones lacked enzyme inhibitory activity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimalarials / chemical synthesis
  • Antimalarials / chemistry
  • Antimalarials / pharmacology*
  • Chalcone / chemical synthesis
  • Chalcone / chemistry
  • Chalcone / pharmacology*
  • Cysteine Endopeptidases / metabolism*
  • Cysteine Proteinase Inhibitors / chemical synthesis
  • Cysteine Proteinase Inhibitors / chemistry
  • Cysteine Proteinase Inhibitors / pharmacology*
  • Humans
  • Isatin / chemical synthesis
  • Isatin / chemistry
  • Isatin / pharmacology
  • Lactones / chemical synthesis
  • Lactones / chemistry
  • Lactones / pharmacology
  • Malaria, Falciparum / drug therapy
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / enzymology*
  • Triazoles / chemical synthesis
  • Triazoles / chemistry
  • Triazoles / pharmacology*

Substances

  • Antimalarials
  • Cysteine Proteinase Inhibitors
  • Lactones
  • Triazoles
  • Chalcone
  • Isatin
  • Cysteine Endopeptidases
  • falcipain