Identification of novel falcipain-2 inhibitors as potential antimalarial agents through structure-based virtual screening

J Med Chem. 2009 Aug 13;52(15):4936-40. doi: 10.1021/jm801622x.

Abstract

The SPECS database was screened against falcipain-2 with two different docking methods to identify structurally diverse nonpeptidic inhibitors. Twenty-eight nonpeptidic molecules among 81 compounds tested were identified as potential inhibitors of falcipain-2. One of the inhibitors exhibited in vitro activity with an IC50 value of 2.4 microM. Furthermore, the similarity analysis has demonstrated that it is feasible to find novel diverse falcipain-2 inhibitors with similar steric shape through virtual screening of large-scale chemical libraries.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimalarials / chemistry*
  • Antimalarials / pharmacology
  • Computer Simulation
  • Cysteine Endopeptidases* / chemistry
  • Cysteine Proteinase Inhibitors / chemistry*
  • Cysteine Proteinase Inhibitors / pharmacology
  • Databases as Topic
  • Models, Molecular
  • Structure-Activity Relationship

Substances

  • Antimalarials
  • Cysteine Proteinase Inhibitors
  • Cysteine Endopeptidases
  • falcipain 2