title: Docking Analysis and Multidimensional Hybrid QSAR Model of 1,4-Benzodiazepine-2,5-Diones as HDM2 Antagonists.
abstract: The inhibitors of p53-HDM2 interaction are attractive molecules for the treatment of wild-type p53 tumors. In order to search more potent HDM2 inhibitors, docking operation with CDOCKER protocol in Discovery Studio 2.1 (DS2.1) and multidimensional hybrid quantitative structure-activity relationship (QSAR) studies through the physiochemical properties obtained from DS2.1 and E-Dragon 1.0 as descriptors, have been performed on 59 1,4-benzodiazepine- 2,5-diones which have p53-HDM2 interaction inhibitory activities. The docking results indicate that π-π interaction between the imidazole group in HIS96 and the aryl ring at 4-N of 1,4-benzodiazepine-2,5-dione may be one of the key factors for the combination of ligands with HDM2. Two QSAR models were obtained using genetic function approximation (GFA) and genetic partial least squares (G/PLS) based on the descriptors obtained from DS2.1 and E-dragon 1.0, respectively. The best model can explain 85.5% of the variance (R (2) adj ) while it could predict 81.7% of the variance (R (2) cv ). With this model, the bioactivities of some new compounds were predicted.
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology (Tianjin University of Science and Technology), Ministry of Education, College of Bioengineering, Tianjin University of Science and Technology, Tianjin 300457, P.R. China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Dai
authors.forename: Nan
authors.initials: N
authors.lastname: Chen
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Heng
authors.initials: H
authors.lastname: Zheng
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhang
authors.forename: Shiru
authors.initials: S
authors.lastname: Jia
authors.forename: Lilong
authors.initials: L
authors.lastname: Dong
authors.forename: Dacheng
authors.initials: D
authors.lastname: Feng
keywords: 1; 4-benzodiazepine-2; 5-diones; CDOCKER; Docking; QSAR; p53-HDM2 interaction