A novel three-dimensional holographic vector of atomic interaction field（3D-HoVAIF） was used to describe the chemical structures of 23 benzoxazinone derivatives as antithrombotic drugs.Here a quantitative structure ...A novel three-dimensional holographic vector of atomic interaction field（3D-HoVAIF） was used to describe the chemical structures of 23 benzoxazinone derivatives as antithrombotic drugs.Here a quantitative structure activity relationship（QSAR） model was built by partial least-squares（PLS） regression.The estimation stability and prediction ability of the model were strictly analyzed by both internal and external validations.The correlation coefficients of established PLS model,leave-one-out（LOO） cross-validation,and predicted values versus experimental ones of external samples were R2=0.899,RCV2=0.854 and Qext2=0.868,respectively.These values indicated that the built PLS model had both favorable estimation stability and good prediction capabilities.Furthermore,the satisfactory results showed that 3D-HoVAIF could preferably express the information related to the biological activity of benzoxazinone derivatives.展开更多
Study on the quantitative structure-activity relationship （QSAR） of 26 compounds, N-[5-（2-furanyl）-2-methyl-4-oxo-4H-thieno[2,3-d]pyrimidin-3-yl]-carboxamide and 3-substituted- 5-（2-furanyl）-2-methyl-3H-thieno[2...Study on the quantitative structure-activity relationship （QSAR） of 26 compounds, N-[5-（2-furanyl）-2-methyl-4-oxo-4H-thieno[2,3-d]pyrimidin-3-yl]-carboxamide and 3-substituted- 5-（2-furanyl）-2-methyl-3H-thieno[2,3-d]pyrimidin-4-ones, with three-dimensional holographic vector of atomic interaction field （3D-HoVAIF） was carried out. SMR-PLS QSAR models have been created and good correlation coefficients and cross-validated correlation coefficients were obtained. The result shows that the models have good prediction capability and favorable stability and the 3D-HoVAIF is applicable to the molecular structural characterization and biological activity prediction.展开更多
20 Typical flavonoids were selected for study on the interaction between them and PIM-1 kinase with the comparative molecular field analysis method（CoMFA） as well as the comparative molecular similarity index analys...20 Typical flavonoids were selected for study on the interaction between them and PIM-1 kinase with the comparative molecular field analysis method（CoMFA） as well as the comparative molecular similarity index analysis method（CoMSIA） based on molecule docking.3D-QSAR models between these flavonoids and receptor PIM-1 kinase were established.The obtained optimal cross-validation correlation coefficient Q2 for CoMFA model was 0.582,and the non-cross-validation correlation coefficient R2 was 0.955;the corresponding values for CoMSIA model were 0.790 and 0.974,respectively.These two models showed fairly fine stability and predictive ability.In addition,molecule docking results revealed the key residues in the receptor cavity and their specific action ways with flavonoids.展开更多
Cancer is one of the most serious issues in human life.Blocking programmed cell death protein 1 and programmed death ligand-1(PD-L1)pathway is one of the great innovations in the last few years,a few numbers of inhibi...Cancer is one of the most serious issues in human life.Blocking programmed cell death protein 1 and programmed death ligand-1(PD-L1)pathway is one of the great innovations in the last few years,a few numbers of inhibitors can be able to block it.(2-Methyl-3-biphenylyl)methanol derivative is one of them.Here,the quantitative structure-activity relationship(QSAR)established twenty(2-methyl-3-biphenylyl)methanol derivatives as the programmed death ligand-1 inhibitors.Density functional theory at the B3LPY/6-31+G(d,p)level was employed to study the chemical structure and properties of the chosen compounds.Highest occupied molecular orbital energy EHOMO,lowest unoccupied molecular orbital energy ELUMO,total energy ET,dipole moment DM,absolute hardnessη,absolute electronegativityχ,softness S,electrophilicityω,energy gap?E,etc.,were observed and determined.Principal component analysis(PCA),multiple linear regression(MLR)and multiple nonlinear regression(MNLR)analysis were carried out to establish the QSAR.The proposed quantitative models and interpreted outcomes of the compounds were based on statistical analysis.Statistical results of MLR and MNLR exhibited the coefficient R^2 was 0.661 and 0.758,respectively.Leave-one-out cross-validation,r_m^2 metric,r_m^2 test,and"Golbraikh&Tropsha’s criteria"analyses were applied for the validation of MLR and MNLR,which indicate two models are statistically significant and well stable with data variation in the external validation towards PD-L1.The obtained results showed that the MNLR model predicts the bioactivity more accurately than MLR,and it may be helpful and supporting for evaluation of the biological activity of PD-L1 inhibitors.展开更多
Considering atomic property vector and atomic correlative function, the 3-dimensional structural vector of atomic property correlation （3D-VAPC）, a novel descriptor,is defined to characterize a 3-dimensional molecul...Considering atomic property vector and atomic correlative function, the 3-dimensional structural vector of atomic property correlation （3D-VAPC）, a novel descriptor,is defined to characterize a 3-dimensional molecular structure by introducing self-adaptability regulation mechanism and the idea of orientating to customers. Characterizing the structures of 25 bisphenol A compounds by this vector, the QSAR models of three kinds of estrogen activities （ER affinities, gene induction and cell proliferation） have high multiple correlation coefficient （Rcum^2=0.933, 0.813, 0.959） and cross verification coefficient （Qcum^2=0.847, 0.953, 0.798） by support vector machine （SVM）, which suits for nonlinear circumstances. The above results show that the models successfully express the correlation between structure and three kinds of estrogen activities. Therefore, 3D-VAPC exactly reflects the molecular structural information and SVM method correctly describes the correlation between information and property of the compounds.展开更多
Canceling grids accommodating probes in comparative molecular field analysis (CoMFA), the idea of flexibleness is introduced into the CoMFA, and in combination with swarm intelligent algorithm which attempts to optimi...Canceling grids accommodating probes in comparative molecular field analysis (CoMFA), the idea of flexibleness is introduced into the CoMFA, and in combination with swarm intelligent algorithm which attempts to optimize distributions of diverse probes around drug molecules, a new 3D-QSAR method is proposed in this context as flexible comparative molecular field analysis (FCoMFA). In preliminary at-tempts to performing QSAR studies on 47 glycogen phosphorylase inhibitors, FCoMFA is employed and confirmed to be potent to exploring ligand-receptor interaction manners at active positions and thus to generating stable and predictable models. Simultaneously by an intuitive graphics regarding probe distribution patterns, impacts of different substituted groups on activities is also given an insight into.展开更多
Twenty-seven novel pyrrolidine-2,4-dione derivatives containing N-substituted phenylhydrazine moiety were synthesized. Their structures were confirmed by IH NMR, 13C NMR and MS. The half effective concentration （ECs0...Twenty-seven novel pyrrolidine-2,4-dione derivatives containing N-substituted phenylhydrazine moiety were synthesized. Their structures were confirmed by IH NMR, 13C NMR and MS. The half effective concentration （ECs0） values of the title compounds against the phytopathogenic fungi Rhizoctonia cerealis were evaluated. Com- pounds 61 and 6q displayed good bioactivity with EC50 values of 1.626 and 2.043 μg/mL, respectively. The 3D quantitative structure activity relationship（3D-QSAR） model of CoMFA was established with reliable cross-validated correlation coefficient q2 value of 0.585 and Noncross-validated correlation coefficient r2 value of 0.971. This model provided a tool for guiding further design and synthesis of novel pyrrolidine-2,4-dione derivatives with high fungicidal activity.展开更多
A three-dimensional quantitative structure-activity relationship(3 D-QSAR) study was conducted to analyze the A1 AR density(Bmax) of 56 3-aroyl-5-substituted thiophene derivatives(ASTDs) in human A1 Chinese hamster ov...A three-dimensional quantitative structure-activity relationship(3 D-QSAR) study was conducted to analyze the A1 AR density(Bmax) of 56 3-aroyl-5-substituted thiophene derivatives(ASTDs) in human A1 Chinese hamster ovary(hA1 CHO) membranes by the comparative molecular field analysis(CoMFA) method. A training set of 45 compounds was used to establish the predictive model, which was verified by the test set of 17 compounds containing template molecule and 5 newly designed molecules. The cross-validation(R2 cv) and non-cross-validation(R2) coefficients of the training set were 0.655 and 0.959, respectively. The model was used to predict the activities of the compounds of the training and test sets, and the results indicated that the models had strong stability and good prediction ability. According to model analysis, the contribution of steric and electrostatic fields was 51.4% and 48.6%, respectively. Based on the 3 D contour maps, five excellent ASTDs agonists were designed, which need to be further verified by biomedical experiments.展开更多
5-Substituted benzylidene 3-acylthiotetronic acids are antifungal.A series of 3-acylthiotetronic acid derivatives with varying substitutions at the 5-position were designed,synthesized,and characterized,based on the b...5-Substituted benzylidene 3-acylthiotetronic acids are antifungal.A series of 3-acylthiotetronic acid derivatives with varying substitutions at the 5-position were designed,synthesized,and characterized,based on the binding pose of 3-acyl thiolactone with the protein C171Q KasA.Fungicidal activities of these compounds were screened against Valsa Mali,Curvularia lunata,Fusarium graminearum,and Fusarium oxysporum f.sp.lycopersici.Most target compounds exhibited excellent fungicidal activities against target fungi at the concentration of 50μg·mL-1.Compounds 11c and 11i displayed the highest activity with a broad spectrum.The median effective concentration(EC50)values of 11c and 11i were 1.9–10.7 and 3.1–7.8μg·mL-1,respectively,against the tested fungi,while the EC50 values of the fungicides azoxystrobin,carbendazim,and fluopyram were respectively 0.30,4.22,and>50μg·mL-1 against V.Mali;6.7,41.7,and 0.18μg·mL-1 against C.lunata;22.4,0.42,and 0.43μg·mL-1 against F.graminearum;and 4.3,0.12,and>50μg·mL-1 against F.oxysporum f.sp.lycopersici.The structures and activities of the target compounds against C.lunata were analyzed to obtain a statistically significant comparative molecular field analysis(CoMFA)model with high prediction abilities(q2=0.9816,r2=0.8060),and its reliability was verified.The different substituents on the benzylidene at the 5-position had significant effects on the activity,while the introduction of a halogen atom at the benzene ring of benzylidene was able to improve the activity against the tested fungi.展开更多
The quantitative structure-activity relationship （QSAR） of 30 acylthiourea analogues was studied by using a three-dimensional holographic vector of atomic interaction field （3D-HoVAIF） to describe their chemical s...The quantitative structure-activity relationship （QSAR） of 30 acylthiourea analogues was studied by using a three-dimensional holographic vector of atomic interaction field （3D-HoVAIF） to describe their chemical structures. The descriptors obtained were screened by stepwise multiple regression （SMR） and a partial least-squares （PLS） regression model was built. The correlation coefficient r^2 of the established model and Leave-One-Out （LOO） Cross-Validation （CV） correlation coefficient q^2 are 0.624 and 0.409, respectively. The model has favorable stability and good prediction capability, and further QSAR analysis showed that hydrophobic interaction has the most important effect on the activity of acylthiourea analogue and 3D-HoVAIF was applicable to the molecular structural characterization and biologicalactivity prediction.展开更多
基金supported by the Natural Science Foundation of Shaanxi Province (2009JQ2005)Foundation of Educational Commission of Shaanxi Province (09JK358) Graduate Innovation Fund of Shaanxi University of Science and Technology
文摘A novel three-dimensional holographic vector of atomic interaction field（3D-HoVAIF） was used to describe the chemical structures of 23 benzoxazinone derivatives as antithrombotic drugs.Here a quantitative structure activity relationship（QSAR） model was built by partial least-squares（PLS） regression.The estimation stability and prediction ability of the model were strictly analyzed by both internal and external validations.The correlation coefficients of established PLS model,leave-one-out（LOO） cross-validation,and predicted values versus experimental ones of external samples were R2=0.899,RCV2=0.854 and Qext2=0.868,respectively.These values indicated that the built PLS model had both favorable estimation stability and good prediction capabilities.Furthermore,the satisfactory results showed that 3D-HoVAIF could preferably express the information related to the biological activity of benzoxazinone derivatives.
基金Supported by the Fund of National High Technology Research and Development Program (863 Program, No. 2006AA02Z312)
文摘Study on the quantitative structure-activity relationship （QSAR） of 26 compounds, N-[5-（2-furanyl）-2-methyl-4-oxo-4H-thieno[2,3-d]pyrimidin-3-yl]-carboxamide and 3-substituted- 5-（2-furanyl）-2-methyl-3H-thieno[2,3-d]pyrimidin-4-ones, with three-dimensional holographic vector of atomic interaction field （3D-HoVAIF） was carried out. SMR-PLS QSAR models have been created and good correlation coefficients and cross-validated correlation coefficients were obtained. The result shows that the models have good prediction capability and favorable stability and the 3D-HoVAIF is applicable to the molecular structural characterization and biological activity prediction.
基金Sponsored by the National Natural Science Foundation of China (No. 20737001,20977046)the National Basic Research Program of China (No. 2009CB42160-4)
文摘20 Typical flavonoids were selected for study on the interaction between them and PIM-1 kinase with the comparative molecular field analysis method（CoMFA） as well as the comparative molecular similarity index analysis method（CoMSIA） based on molecule docking.3D-QSAR models between these flavonoids and receptor PIM-1 kinase were established.The obtained optimal cross-validation correlation coefficient Q2 for CoMFA model was 0.582,and the non-cross-validation correlation coefficient R2 was 0.955;the corresponding values for CoMSIA model were 0.790 and 0.974,respectively.These two models showed fairly fine stability and predictive ability.In addition,molecule docking results revealed the key residues in the receptor cavity and their specific action ways with flavonoids.
基金the Natural Science Foundation of Jiangsu Province(BK20181128)333 Project of Jiangsu Province(BRA2016518)Jiangsu Provincial Medical Youth Talent(QNRC2016626)。
文摘Cancer is one of the most serious issues in human life.Blocking programmed cell death protein 1 and programmed death ligand-1(PD-L1)pathway is one of the great innovations in the last few years,a few numbers of inhibitors can be able to block it.(2-Methyl-3-biphenylyl)methanol derivative is one of them.Here,the quantitative structure-activity relationship(QSAR)established twenty(2-methyl-3-biphenylyl)methanol derivatives as the programmed death ligand-1 inhibitors.Density functional theory at the B3LPY/6-31+G(d,p)level was employed to study the chemical structure and properties of the chosen compounds.Highest occupied molecular orbital energy EHOMO,lowest unoccupied molecular orbital energy ELUMO,total energy ET,dipole moment DM,absolute hardnessη,absolute electronegativityχ,softness S,electrophilicityω,energy gap?E,etc.,were observed and determined.Principal component analysis(PCA),multiple linear regression(MLR)and multiple nonlinear regression(MNLR)analysis were carried out to establish the QSAR.The proposed quantitative models and interpreted outcomes of the compounds were based on statistical analysis.Statistical results of MLR and MNLR exhibited the coefficient R^2 was 0.661 and 0.758,respectively.Leave-one-out cross-validation,r_m^2 metric,r_m^2 test,and"Golbraikh&Tropsha’s criteria"analyses were applied for the validation of MLR and MNLR,which indicate two models are statistically significant and well stable with data variation in the external validation towards PD-L1.The obtained results showed that the MNLR model predicts the bioactivity more accurately than MLR,and it may be helpful and supporting for evaluation of the biological activity of PD-L1 inhibitors.
基金This work was supported by the Natural Science Foundation of CQ CSTC (No. 2006BB5177)
文摘Considering atomic property vector and atomic correlative function, the 3-dimensional structural vector of atomic property correlation （3D-VAPC）, a novel descriptor,is defined to characterize a 3-dimensional molecular structure by introducing self-adaptability regulation mechanism and the idea of orientating to customers. Characterizing the structures of 25 bisphenol A compounds by this vector, the QSAR models of three kinds of estrogen activities （ER affinities, gene induction and cell proliferation） have high multiple correlation coefficient （Rcum^2=0.933, 0.813, 0.959） and cross verification coefficient （Qcum^2=0.847, 0.953, 0.798） by support vector machine （SVM）, which suits for nonlinear circumstances. The above results show that the models successfully express the correlation between structure and three kinds of estrogen activities. Therefore, 3D-VAPC exactly reflects the molecular structural information and SVM method correctly describes the correlation between information and property of the compounds.
基金Supported by National High Technology (863) Program (Grant No. 2006AA02Z312)the State Key Laboratory of Chemo/Biosensing and Chemometrics Foundation (Grant No. 0501201)Chongqing University Innovation Fund (Grant No. 030506)
文摘Canceling grids accommodating probes in comparative molecular field analysis (CoMFA), the idea of flexibleness is introduced into the CoMFA, and in combination with swarm intelligent algorithm which attempts to optimize distributions of diverse probes around drug molecules, a new 3D-QSAR method is proposed in this context as flexible comparative molecular field analysis (FCoMFA). In preliminary at-tempts to performing QSAR studies on 47 glycogen phosphorylase inhibitors, FCoMFA is employed and confirmed to be potent to exploring ligand-receptor interaction manners at active positions and thus to generating stable and predictable models. Simultaneously by an intuitive graphics regarding probe distribution patterns, impacts of different substituted groups on activities is also given an insight into.
基金Supported by the National High Technology Research and Development Program of China（No.2011AA10A206）, the National Key Technologies R＆D Program of China（No.2011BAE06B04）, the Science ＆ Technology Pillar Program of Jiangsu Province, China（No.BE2012371）, the National Natural Science Foundation of China（No.31171889） and the Fundamental Research Funds for the Central Universities of China（No.KYZ201223）.
文摘Twenty-seven novel pyrrolidine-2,4-dione derivatives containing N-substituted phenylhydrazine moiety were synthesized. Their structures were confirmed by IH NMR, 13C NMR and MS. The half effective concentration （ECs0） values of the title compounds against the phytopathogenic fungi Rhizoctonia cerealis were evaluated. Com- pounds 61 and 6q displayed good bioactivity with EC50 values of 1.626 and 2.043 μg/mL, respectively. The 3D quantitative structure activity relationship（3D-QSAR） model of CoMFA was established with reliable cross-validated correlation coefficient q2 value of 0.585 and Noncross-validated correlation coefficient r2 value of 0.971. This model provided a tool for guiding further design and synthesis of novel pyrrolidine-2,4-dione derivatives with high fungicidal activity.
基金supported by the National Natural Science Foundation of China (21676292,21075138)special fund of State Key Laboratory of Structure Chemistry (2016028)。
文摘A three-dimensional quantitative structure-activity relationship(3 D-QSAR) study was conducted to analyze the A1 AR density(Bmax) of 56 3-aroyl-5-substituted thiophene derivatives(ASTDs) in human A1 Chinese hamster ovary(hA1 CHO) membranes by the comparative molecular field analysis(CoMFA) method. A training set of 45 compounds was used to establish the predictive model, which was verified by the test set of 17 compounds containing template molecule and 5 newly designed molecules. The cross-validation(R2 cv) and non-cross-validation(R2) coefficients of the training set were 0.655 and 0.959, respectively. The model was used to predict the activities of the compounds of the training and test sets, and the results indicated that the models had strong stability and good prediction ability. According to model analysis, the contribution of steric and electrostatic fields was 51.4% and 48.6%, respectively. Based on the 3 D contour maps, five excellent ASTDs agonists were designed, which need to be further verified by biomedical experiments.
基金This work was financially supported in part by the National Natural Science Foundation of China(31901906)the Opening Project of Shanghai Key Laboratory of Chemical Biology,the Natural Science Foundation of Anhui Province,China(1808085QC71)+1 种基金the Natural Science Foundation of Anhui Education Department(KJ2016A834)the US Department of Agriculture(USDA:HAW5032-R).
文摘5-Substituted benzylidene 3-acylthiotetronic acids are antifungal.A series of 3-acylthiotetronic acid derivatives with varying substitutions at the 5-position were designed,synthesized,and characterized,based on the binding pose of 3-acyl thiolactone with the protein C171Q KasA.Fungicidal activities of these compounds were screened against Valsa Mali,Curvularia lunata,Fusarium graminearum,and Fusarium oxysporum f.sp.lycopersici.Most target compounds exhibited excellent fungicidal activities against target fungi at the concentration of 50μg·mL-1.Compounds 11c and 11i displayed the highest activity with a broad spectrum.The median effective concentration(EC50)values of 11c and 11i were 1.9–10.7 and 3.1–7.8μg·mL-1,respectively,against the tested fungi,while the EC50 values of the fungicides azoxystrobin,carbendazim,and fluopyram were respectively 0.30,4.22,and>50μg·mL-1 against V.Mali;6.7,41.7,and 0.18μg·mL-1 against C.lunata;22.4,0.42,and 0.43μg·mL-1 against F.graminearum;and 4.3,0.12,and>50μg·mL-1 against F.oxysporum f.sp.lycopersici.The structures and activities of the target compounds against C.lunata were analyzed to obtain a statistically significant comparative molecular field analysis(CoMFA)model with high prediction abilities(q2=0.9816,r2=0.8060),and its reliability was verified.The different substituents on the benzylidene at the 5-position had significant effects on the activity,while the introduction of a halogen atom at the benzene ring of benzylidene was able to improve the activity against the tested fungi.
基金supported by the National High-tech Research Program (the "863" Program, No. 2006AA02Z312)Innovative Group Program for Graduates of Chongqing University, Science and Innovation Fund (No. 200711C1A0010260)
文摘The quantitative structure-activity relationship （QSAR） of 30 acylthiourea analogues was studied by using a three-dimensional holographic vector of atomic interaction field （3D-HoVAIF） to describe their chemical structures. The descriptors obtained were screened by stepwise multiple regression （SMR） and a partial least-squares （PLS） regression model was built. The correlation coefficient r^2 of the established model and Leave-One-Out （LOO） Cross-Validation （CV） correlation coefficient q^2 are 0.624 and 0.409, respectively. The model has favorable stability and good prediction capability, and further QSAR analysis showed that hydrophobic interaction has the most important effect on the activity of acylthiourea analogue and 3D-HoVAIF was applicable to the molecular structural characterization and biologicalactivity prediction.
