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

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.

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Correspondence to Julio Caballero.

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Caballero, J., Vergara-Jaque, A., Fernández, M. et al. Docking and quantitative structure–activity relationship studies for sulfonyl hydrazides as inhibitors of cytosolic human branched-chain amino acid aminotransferase. Mol Divers 13, 493–500 (2009). https://doi.org/10.1007/s11030-009-9140-1

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Keywords

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