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3D-QSAR Study on Apicidin Inhibit Histone Deacetylase 预览

3D-QSAR Study on Apicidin Inhibit Histone Deacetylase
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摘要 For Histone Deacetylase (HDAC) Inhibitor, four 3D-QSAR models for four types of different activities, were constructed.The cross-valldated q^2 value of CoMFA Model 1 is 0.624 and the noncross-validated r2 value is 0.939. The cross-validated q^2 value of Model 2 for training set is 0.652 and the noncross-validated r^2 value is 0.963. The cross-validated q^2 value for Model 3 is 0.713, with noncross-validated r^2 value 0.947. The crossvalidated q2 value for Model 4 is 0.566 with noncross-validated r^2 value 0.959. Their predicted abilities were validated by different test sets which did not include in training set. Then the relationship between substituents and activities was analyzed by using these models and the main influence elements in different positions (positions 8 and 14) were found. The polar donor electron group of position 8 could increase the activity of inhibition of HDAC, because it could form chelation with the catalytic Zn. Suitable bulk and positive groups at position 14 are favorable to anti-HDAC activity. These models could web interpret the relationship between inhibition activity and apicidin structure affording us important information for structurebased drug design. For Histone Deacetylase (HDAC) Inhibitor, four 3D-QSAR models for four types of different activities,were constructed. The cross-validated q 2 value of CoMFA Model 1 is 0.624 and the noncross-validated r 2 value is 0.939. The cross-validated q 2 value of Model 2 for training set is 0.652 and the noncross-validated r 2 value is 0.963. The cross-validated q 2 value for Model 3 is 0.713,with noncross-validated r 2 value 0.947. The cross-validated q 2 value for Model 4 is 0.566 with noncross-validated r 2 value 0.959. Their predicted abilities were validated by different test sets which did not include in training set. Then the relationship between substituents and activities was analyzed by using these models and the main influence elements in different positions (positions 8 and 14) were found. The polar donor electron group of position 8 could increase the activity of inhibition of HDAC,because it could form chelation with the catalytic Zn. Suitable bulk and positive groups at position 14 are favorable to anti-HDAC activity. These models could well interpret the relationship between inhibition activity and apicidin structure affording us important information for structure-based drug design.
作者 陈海峰 康九红 李强 曾宝珊 姚小军 范波涛 袁身刚 Panay,A. Doucet,J.P. CHEN,Hai-Feng a KANG,Jiu-Hong b LI,Qiang aZENG,Bao-Shan a YAO,Xiao-Jun c FAN,Bo-Tao cYUAN,Shen-Gang ,a Panay,A. c Doucet,J. P. c aKey Laboratory of Computer Chemistry,Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences,Shanghai 200032,China bSchool of Life Science,Lanzou University,Lanzou,Gansu 730000,China cITODYS,CNRS UMR 7086,Université Paris 7,1,rue Guy de la Brosse,75005 Paris,France
出处 《中国化学:英文版》 SCIE CAS CSCD 2003年第12期 1596-1607,共12页 Chinese Journal of Chemistry
基金 ProjectsupportedbytheMinisterofScienceandTechnologyofChina (No .2 0 0 2AA2 3 10 11) ,theNationalNaturalScienceFoundationofChina (No .2 0 0 73 0 5 8) ,theScienceandTechnologyCommitteeofShanghai (No .0 2DJ14 0 13 ) ,ChineseAcademyofSciences NationalCentero
关键词 3D-QSAR 组蛋白脱乙酰基酶 抑制剂 COMFA 药物设计 DNA 分子模型 histone deacetylase inhibitor,CoMFA,3D-QSAR
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