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

作者：Caballero Julio^*; Vergara Jaque Ariela; Fernandez Michael; Coll Deysma

来源：Molecular Diversity, 2009, 13(4): 493-500.

DOI：10.1007/s11030-009-9140-1

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

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 (IC(50)) 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.

• 出版日期2009-11
• 单位上海生物信息技术研究中心