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Molecular Diversity

, Volume 13, Issue 4, pp 493–500 | Cite as

Docking and quantitative structure–activity relationship studies for sulfonyl hydrazides as inhibitors of cytosolic human branched-chain amino acid aminotransferase

  • Julio CaballeroEmail author
  • Ariela Vergara-Jaque
  • Michael Fernández
  • Deysma Coll
Full Length Paper

Abstract

We have performed the docking of sulfonyl hydrazides complexed with cytosolic branched-chain amino acid aminotransferase (BCATc) to study the orientations and preferred active conformations of these inhibitors. The study was conducted on a selected set of 20 compounds with variation in structure and activity. In addition, the predicted inhibitor concentration (IC50) of the sulfonyl hydrazides as BCAT inhibitors were obtained by a quantitative structure–activity relationship (QSAR) method using three-dimensional (3D) vectors. We found that three-dimensional molecule representation of structures based on electron diffraction (3D-MoRSE) scheme contains the most relevant information related to the studied activity. The statistical parameters [cross-validate correlation coefficient (Q 2 = 0.796) and fitted correlation coefficient (R 2 = 0.899)] validated the quality of the 3D-MoRSE predictive model for 16 compounds. Additionally, this model adequately predicted four compounds that were not included in the training set.

Keywords

Branched-chain amino acid aminotransferase inhibitors Molecular docking Quantitative structure–activity relationships Three-dimensional descriptors 

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Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Julio Caballero
    • 1
    Email author
  • Ariela Vergara-Jaque
    • 1
  • Michael Fernández
    • 2
    • 3
  • Deysma Coll
    • 4
  1. 1.Centro de Bioinformática y Simulación Molecular, Facultad de Ingeniería en BioinformáticaUniversidad de TalcaTalcaChile
  2. 2.Molecular Modeling Group, Center for Biotechnological StudiesUniversity of MatanzasMatanzasCuba
  3. 3.Department of Bioscience and BioinformaticsKyushu Institute of Technology (KIT)FukuokaJapan
  4. 4.Center for Natural Products Study, Faculty of ChemistryUniversity of HavanaHavanaCuba

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