docking analysis and multidimensional hybrid qsar model of 1,4-benzodiazepine-2,5-diones as hdm2 antagonists

نویسندگان

yujie dai 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.

nan chen 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.

qiang wang 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.

heng zheng school of life science and technology, china pharmaceutical university, nanjing 210009, p.r. china.

چکیده

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 () while it could predict 81.7% of the variance (). with this model, the bioactivities of some new compounds were predicted.

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Docking Analysis and Multidimensional Hybrid QSAR Model of 1,4-Benzodiazepine-2,5-Diones as HDM2 Antagonists

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 desc...

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Docking Analysis and Multidimensional Hybrid QSAR Model of 1,4-Benzodiazepine-2,5-Diones as HDM2 Antagonists

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 desc...

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Docking Analysis and Multidimensional Hybrid QSAR Model of 1,4-Benzodiazepine-2,5-Diones as HDM2 Antagonists

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عنوان ژورنال:
the iranian journal of pharmaceutical research

جلد ۱۱، شماره ۳، صفحات ۸۰۷-۸۳۰

کلمات کلیدی
[ ' p 5 3 ' , ' h d m 2 i n t e r a c t i o n ' , ' d o c k i n g ' , ' q s a r ' , 1 , 4 , ' b e n z o d i a z e p i n e ' , 2 , 5 , ' d i o n e s ' , ' c d o c k e r ' ]

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