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QSAR and Pharmacophore Studies of Thiazolidine-4-carboxylic Acid Derivatives as Novel Influenza Neuraminidase Inhibitors Using HQSAR, topomer comfa and CoMSIA

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Chinese Journal of Structural Chemistry 2013年第5期32卷 744-750页

作者：孙家英王建超梅虎 Department of Chemistry and Chemical Engineering Sichuan University of Arts and Science College of Bioengineering Chongqing University

In order to understand the chemical-biological interactions governing their activities toward neuraminidase （NA）, QSAR models of 28 thiazolidine-4-carboxylic acid derivatives with inhibitory influenza A virus were developed. The obtained HQSAR （hologram quantitative structure activity relationship）, topomer comfa and CoMSIA （comparative molecular similarity indices analysis） models were robust and had good exterior predictive capabilities. Moreover, QSAR modeling results elucidated that hydrogen bonds highly contributed to the inhibitory activity, then electrostatic and hydrophobic factors. Squared multiple correlation coefficients （R2） of HQSAR, topomer comfa and CoMSIA models were 0.994, 0.978 and 0.996, respectively. Squared cross-validated correlation coefficients （Q2） of HQSAR, topomer comfa and CoMSIA models were in turn 0.951, 919 and 0.820. Furthermore, squared multiple correlation coefficients for the test set （R2test） of HQSAR, comfa and CoMSIA models were 0.879, 0.912 and 0.953, respectively. Squared cross-validated correlation coefficients for the test set （Q2ext） of HQSAR, topomer comfa and CoMSIA models were 0.867, 0.884 and 0.899, correspondingly.

关键词： QSAR thiazolidine-4-carboxylic acid derivatives,HQSAR topomer comfa CoMSIA

基于topomer comfa技术的AKR1C3选择性抑制剂的研究

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化学研究与应用 2023年第2期35卷 370-378页

作者：吴峥吴伟俊覃文亭覃馨玉邵侃何温靖广西医科大学药学院广西南宁530021

醛酮还原酶(AKR1C3)是治疗去势抵抗性前列腺癌(CRPC)的重要靶点,寻找高选择性的AKR1C3抑制剂是该靶点研究的热点和难点。本文采用topomer comfa技术,对46个AKR1C3选择性抑制剂进行三维定量构效关系研究,得到3D-QSAR模型,其交互验证系数q... 详细信息

醛酮还原酶(AKR1C3)是治疗去势抵抗性前列腺癌(CRPC)的重要靶点,寻找高选择性的AKR1C3抑制剂是该靶点研究的热点和难点。本文采用topomer comfa技术,对46个AKR1C3选择性抑制剂进行三维定量构效关系研究,得到3D-QSAR模型,其交互验证系数q2为0.59,非交叉相关系数r^(2)为0.918,主成分数N为5,q^(2)_(p red)为0.98,结果表明该模型有较好的预测能力。采用topomer Search技术在Decoy数据库中进行R基团的筛选,选择RN值最大的10个Ra片段和8个Rb片段进行拼接,获得7个活性预测值高于模板分子,3个活性预测值与模板分子相当的化合物。最后,用分子对接技术研究所设计的新化合物与AKR1C3的作用模式,发现化合物N05和N06可以同时与关键酶催化位点(OS)和选择性口袋SP1中的氨基酸残基Tyr55和Asn167发生作用,说明所设计的AKR1C3抑制剂具有较高的AKR1C3选择性。

关键词： AKR1C3抑制剂 topomer comfa topomer Search 分子对接

基于topomer comfa方法的苯并呋喃类褪黑激素受体拮抗药的三维定量构效关系研究

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中国药师 2020年第10期23卷 1910-1914页

作者：方明阳梁佳龙孙智勇王菲中国人民解放军陆军第946医院新疆伊宁835000 空军军医大学药学院陕西省食品药品监督检验研究院

目的:建立苯丙呋喃类化合物褪黑激素受体拮抗药的三维定量构效关系(3D-QSAR)模型。方法:使用SYBYLx2.1.1软件中的topomer comfa模块对29个苯并呋喃类分子进行三维定量构效关系分析。保留母核结构切割后得到了3个R基片段,分别计算所产生... 详细信息

目的:建立苯丙呋喃类化合物褪黑激素受体拮抗药的三维定量构效关系(3D-QSAR)模型。方法:使用SYBYLx2.1.1软件中的topomer comfa模块对29个苯并呋喃类分子进行三维定量构效关系分析。保留母核结构切割后得到了3个R基片段,分别计算所产生的立体场与静电场。结果:对于褪黑激素受体1(MT1)和褪黑激素受体2(MT2)分别建立了可靠、合理的topomer comfa模型(MT1:q2=0.650,r2=0.924;MT2:q2=0.486,r2=0.920)。结论:建立的topomer comfa模型阐明了苯并呋喃类化合物分子对褪黑激素受体的生物活性的影响因素。通过分析实验化合物MT1与MT2的活性值比值(MT1/MT2),发现R2基团的电负性变化可能使该类化合物对两种受体表现出不同选择性。

关键词：褪黑激素受体三维定量构效关系 topomer comfa

香豆素衍生物AChE抑制剂的3D-QSAR研究

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广州化工 2024年第8期52卷 79-82页

作者：李泽鹏孔唯龙杨绍淇余丽丽西安医学院药学院药物研究所西安市多靶协同抗高血压创新药物研制重点实验室陕西西安710021

采用topomer comfa方法研究了44种香豆素衍生物AChE抑制剂的三维定量构效关系D-QSAR模型。建立的Topmer comfa模型的交互验证相关系数q^(2)为0.606,拟合相关系r^(2)=0.996,标准估计误差SEE=0.046,Fisher检验值F=891.096,由此可见该模型... 详细信息

采用topomer comfa方法研究了44种香豆素衍生物AChE抑制剂的三维定量构效关系D-QSAR模型。建立的Topmer comfa模型的交互验证相关系数q^(2)为0.606,拟合相关系r^(2)=0.996,标准估计误差SEE=0.046,Fisher检验值F=891.096,由此可见该模型是有效的。通过topomer comfa模型三维等势图揭示了结构对活性的影响。并采用分子对接研究了配体和受体蛋白之间的结合。该模型为进一步探索黄酮类衍生物作为AChE抑制的构效关系,以及该类分子的结构设计奠定理论基础。

关键词： topomer comfa AChE抑制剂分子对接香豆素衍生物

Drug Design,Molecular Docking,and ADMET Prediction of CCR5 Inhibitors Based on QSAR Study

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Chinese Journal of Structural Chemistry 2022年第2期41卷 1-13,I0007页

作者： TONG Jian-Bo ZHANG Xing BIAN Shuai LUO Ding College of Chemistry and Chemical Engineering Shaanxi University of Science and TechnologyXi'an 110021China Shaanxi Key Laboratory of Chemical Additives for Industry Shaanxi University of Science and TechnologyXi'an 710021China

The chemokine receptor CCR5 is a main and necessary co-receptor for which HIV can recognize and enter the cells,and has been identified as a potential new target for the design of new anti-HIV therapeutic *** active CCR5 inhibitors can prevent HIV-1 from entering target cells and block the process of *** this study,HQSAR and topomer Co MFA methods were used to establish QSAR models for 75 1-(3,3-diphenylpropyl)-piperidinyl and urea derivatives,and cross-validation and non-cross-validation were performed on the generated *** models with good statistical parameters and reliable prediction capabilities are obtained:(topomer Co MFA:q2 = 0.687,r2 = 0.868,r2 pred = 0.623;HQSAR:q2 = 0.781,r2 = 0.921,r2 pred = 0.636).Contour maps and color code maps provide a lot of useful information for determining structural requirements that affect *** search technology was used for virtual screening and molecular ***-dock method and ADMET technology were used to conduct molecular docking,oral bioavailability and toxicity prediction of the designed drug *** showed that A/ASN425,A/GLY198 and A/TRP427 may be the potential active residues of CCR5 inhibitors evaluated in this study,with 40 newly designed 1-(3,3-diphenylpropyl)-piperidinyl and urea derivatives which have the main ADMET properties and can be used as a reliable anti-HIV *** results provide a certain theoretical basis for the experimental verification of new compounds in the future.

关键词： HIV CCR5 inhibitors topomer comfa HQSAR ADMET

QSAR Study and Molecular Design of Isoquinolone Derivative JNK1 Inhibitors

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Chinese Journal of Structural Chemistry 2021年第12期40卷 1586-1594,1551页

作者： TONG Jian-Bo XIAO Xue-Chuna LUO Ding XU Hai-Yin WANG Jie College of Chemistry and Chemical Engineering Shaanxi University of Science and TechnologyXi'an 710021China Shaanxi Key Laboratory of Chemical Additives for Industry Xi'an 710021China

JNK1 is a drug target for the treatment of type 2 diabetes,and it plays a key mediator role in metabolic *** this paper,holographic quantitative structure-activity relationship(HQSAR)technology and topomer comparative molecular field analysis(topomer comfa)technology are used to analyze the quantitative structure-activity relationship(QSAR)of 39 isoquinolone *** cross validation correlation coefficient(q^(2))is 0.696(topomer comfa)and 0.826(HQSAR),and the non-cross validation correlation coefficient(r^(2))is 0.935(topomer comfa)and 0.987(HQSAR).The results showed that the models have good stability and predictive *** topomer search module was applied to define high contribution fragments in the ZINC database,designing 20 new isoquinolone compounds with theoretically high inhibitory *** molecular docking was carried out to explore the interaction between the ligand and target JNK1 *** study can provide a theoretical basis for the design of new JNK1 inhibitors.

关键词： topomer comfa HQSAR molecular docking isoquinolone derivatives molecular design

Molecular Modeling Studies of 4-Hydroxyamino α-Pyranone Carboxamide Analogues as Hepatitis C Virus Inhibitor Using 3D-QSAR and Molecular Docking

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Chinese Journal of Structural Chemistry 2020年第6期39卷 1135-1145页

作者： TONG Jian-Bo WU Lu-Yang LEI Shan WANG Tian-Hao MA Yang-Min College of Chemistry and Chemical Engineering Shaanxi University of Science and TechnologyXi'an 710021China Shaanxi Key Laboratory of Chemical Additives for Industry Xi'an 710021China

In this paper, 42 4-hydroxyamino α-pyranone carboxamide analogues as Hepatitis C Virus(HCV) inhibitor 3 D-QSAR model was built based on topomer comfa. The non-cross-validation(r2), cross-validation(q2), correlation coefficient of external validation(Q ext2), non-cross validated standard error(SD), standard error of prediction(SDCV) and F are 0.909, 0.615, 0.967, 0.13, 0.28 and 37.287, respectively. The obtained topomer comfa model has good estimation stability and prediction capability. topomer Search was employed as a tool for virtual screening in lead-like compounds in the ZINC database. Then, 6 R1 groups and 4 R2 groups with higher contribution values were employed to alternately substitute for the R1 and R2 of the template compound 21 with the highest bioactivity. As a result, 22 new molecules with higher activity than that of the template molecule were designed successfully. The topomer Search technology could be effectively applied to screen and design new 4-hydroxyamino α-pyranone carboxamide analogues. The molecular docking method was also used to study the interactions of these drugs by docking the ligands into HCV active site, which revealed the likely bioactive conformations. This study showed extensive interactions between the 4-hydroxyamino α-pyranone carboxamide analogues and the active sites of HCV(residues TYR466, GLN384, TYR383 and ASP335). The design of potent new inhibitors of HCV can get useful insights from these results.

关键词： 3D-QSAR 4-hydroxyamino a-pyranone carboxamide analogues topomer comfa molecule design molecular docking

Computational Analysis of Artimisinin Derivatives on the Antitumor Activities

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Natural Products and Bioprospecting 2017年第6期7卷 433-443页

作者： Hui Liu Xingyong Liu Li Zhang School of Chemical Engineering Sichuan University of Science&EngineeringZigongChina

The study on antitumor activities of artemisinin and its derivatives has been closely focused on in recent ***,2D and 3D QSAR analysis was performed on the basis of a series of artemisinin derivatives with known bioactivities against the non-small-cell lung adenocarcinoma A549 *** QSAR models were successfully established by CoMSIA,comfa,topomer comfa and HQSAR approaches with respective characteristic values q^(2)=0.567,R2=0.968,ONC=5;q^(2)=0.547,R2=0.980,ONC=7;q^(2)=0.559,R^(2)=0.921,ONC=7 and q^(2)=0.527,R^(2)=0.921,ONC=*** predictive ability of CoMSIA with r^(2)=0.991 is the best one compared with the other three approaches,such as comfa(r^(2)=0.787),topomer comfa(r^(2)=0.819)and HQSAR(r^(2)=0.743).The final QSAR models can provide guidance in structural modification of artemisinin derivatives to improve their anticancer activities.

关键词： QSAR comfa CoMSIA topomer comfa HQSAR Artemisinin

黄酮类化合物对CYP1A1酶抑制活性的3D-定量构效关系研究

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中草药 2021年第5期52卷 1343-1350页

作者：何庆陈萍萍李昊吕沐瀚梁思成齐晓怡熊霞葛广波西南医科大学附属医院皮肤科四川泸州646000 西南医科大学附属医院消化内科四川泸州646000 上海中医药大学交叉科学研究院上海201203

目的通过构建3D-定量构效关系(quantitativestructure-activityrelationship,QSAR)模型,研究黄酮类化合物对细胞色素P450酶1A1(cytochrome P450 1A1,CYP1A1)的抑制活性。方法借助topomer comfa方法开展黄酮类化合物结构-CYP1A1抑制活性构效关系研究;通过体外孵育体系对化合物CYP1A1抑制活性进行评价,开展预测模型验证和优化;通过分子对接技术探究黄酮类化合物抑制CYP1A1活性的作用机制。结果构建的3D-QSAR模型交叉验证相关系数(q2)为0.800,非交互验证系数(r^(2))为0.9650,外部验证的相关系数(rpred^(2))为0.9567,表现出良好的稳定性和预测能力。利用该模型预测9种黄酮类化合物的CYP1A1抑制活性,实验值与预测值的相关系数r^(2)为0.832 8。分子对接结果显示,黄酮类化合物能与CYP1A1空腔内的THR497、ASN222、ASN255、SER116和ASP313等残基形成氢键,影响该类化合物的CYP1A1抑制活性大小。结论构建的模型具有良好预测能力与稳定性,为设计高活性分子提供理论参考,为新型CYP1A1酶抑制剂的开发提供新的思路。

关键词：细胞色素P450酶1A1 黄酮类化合物酶抑制剂定量构效关系 topomer comfa 分子对接