CoMFA and HQSAR of acylhydrazide cruzain inhibitors

Bioorg Med Chem Lett. 2002 Jun 3;12(11):1537-41. doi: 10.1016/s0960-894x(02)00189-0.


An approach combining CoMFA and HQSAR methods was used to describe QSAR models for a series of cruzain inhibitors having the acylhydrazide framework. A CoMFA study using two alignment orientations (I and II), three different probe atoms and changes of the lattice spacing (1 and 2 A) was performed. Alignment II and an sp3 probe carbon atom yielded good cross-validation (q2=0.688) employing lattice spacing of 1 A. The best HQSAR model was generated using atoms, bond, and connectivity as fragment distinction and fragment size default (4-5) showing similar cross-validated value of CoMFA (q2=0.689). Based upon the information derived from CoMFA and HQSAR, we have identified some key features that may be used to design new acylhydrazide derivatives that may be more potent cruzain inhibitors.

Publication types

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

MeSH terms

  • Animals
  • Cysteine Endopeptidases / metabolism
  • Cysteine Proteinase Inhibitors / chemistry*
  • Cysteine Proteinase Inhibitors / pharmacology*
  • Drug Design
  • Hydrazines / chemistry*
  • Hydrazines / pharmacology*
  • Imaging, Three-Dimensional / instrumentation
  • Imaging, Three-Dimensional / methods
  • Inhibitory Concentration 50
  • Ligands
  • Models, Molecular
  • Molecular Conformation
  • Protozoan Proteins / antagonists & inhibitors*
  • Protozoan Proteins / metabolism
  • Quantitative Structure-Activity Relationship
  • Trypanosoma cruzi / enzymology


  • Cysteine Proteinase Inhibitors
  • Hydrazines
  • Ligands
  • Protozoan Proteins
  • Cysteine Endopeptidases
  • cruzain, Trypanosoma cruzi