Electrochemical degradation of sulfamethoxazole(SMX)and its metabolite acetyl-sulfamethoxazole(AcSMX)by Ti/SnO_(2)-Sb/Er-PbO_(2) were investigated.Results indicated that the electrochemical degradation of SMX and Ac-S...Electrochemical degradation of sulfamethoxazole(SMX)and its metabolite acetyl-sulfamethoxazole(AcSMX)by Ti/SnO_(2)-Sb/Er-PbO_(2) were investigated.Results indicated that the electrochemical degradation of SMX and Ac-SMX followed pseudo-first-order kinetics.The rate constants of SMX and Ac-SMX were 0.268 and 0.072 min-1 at optimal curre nt density of 10 and 14 mA/cm^(2),respectively.Transformation products of SMX and Ac-SMX were identified and the possible degradation pathways,including the cleavage of S-N bond,opening ring of isoxazole and nitration of amino group,were proposed.Total organic carbon removal of SMX was nearly 63.2%after 3 h electrochemical degradation.22.4%nitrogen of SMX was trans formed to NO_(3)-,and 98.8%sulfur of SMX was released as SO_(4)2-.According to quantitative structureactivity relationship model,toxicities of SMX and Ac-SMX to aquatic organisms significantly decreased after electrochemical degradation.Electric energy consumption for 90%SMX and Ac-SMX degradation was determined to be 0.58-8.97 and 6.88-44.19 Wh/L at different experimental conditions,respectively.Compared with parent compound SMX,the metabolite Ac-SMX is more refractory and toxic,which emphasizes the importance of taking its metabolites into account when investigating the disposal of pharmaceuticals from wastewater.展开更多
The artificial neural network (ANN) model with back-propagation of error is used to study the quantitative structure-activity relationship of para-substituted phenol derivatives between the biological activity and the...The artificial neural network (ANN) model with back-propagation of error is used to study the quantitative structure-activity relationship of para-substituted phenol derivatives between the biological activity and the physicochemical property parameters. Network parameters are optimized, and an empirical rule for dynamically adjusting the network’s learning rate is proposed to improve the network’s performance. The results showthat the three-layer ANN model gives satisfactory performance, with f(x)=1/(1+exp(-x)) as the network node’s input-output transformation function and the number of hidden nodes 10. The network gives the mean square error (rose) of 0.036 when predicting the biological activity of 26 para-substituted phenol derivatives. This result compares favourably with that obtained by the conventional methods.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
An old drug with a new use can significantly reduce the cost and time for new drug research and development. MAPK （Mitogen-activated protein kinase） plays a very important key role in signal transduction pathways of...An old drug with a new use can significantly reduce the cost and time for new drug research and development. MAPK （Mitogen-activated protein kinase） plays a very important key role in signal transduction pathways of cell proliferation and differentiation. According to the statistics, there are about 30% persons who suffered from cancers related to the MAPK signal transduction pathways. Therefore, many researchers are focused on blocking these pathways in cancers therapies. Ras/Raf/MEK/ERK, however, is one of very important pathways among MAPK message transduction pathways. More and more information about MEK protein inhibitors are unveiled in several recent years. In the present study, the authors utilized MEK inhibitors which were already published and their activities were available to construct 2D-QSAR model by using CADD （multiple linear regression）. Then, the authors searched certified FDA drugs （Drugs@FDA 6184 drugs） making preliminary screening. The secondary screening on 3D structures were followed by using Docking, Scoring and Pharmacophore analysis to find out most suitable MEK inhibitors to become a fundamental database in drug discovery. The results are shown the ALogP, number of aromatic rings, number of hydrogen bond acceptors and number of hydrogen bond donors are all in positive correlation. According to the equation from 2D-QSAR model, the results conform to the previous description.展开更多
The catalysis of chloridized metalloporphyrins in the oxidation of cyclohexane to adipic acid was systemati-cally investigated.The turnover numbers(TON)data of 19 catalysts were obtained experimentally under optimal r...The catalysis of chloridized metalloporphyrins in the oxidation of cyclohexane to adipic acid was systemati-cally investigated.The turnover numbers(TON)data of 19 catalysts were obtained experimentally under optimal reac-tion conditions,and 2.4x106 TON for T(o-Cl)PP-MnIIICl catalyst at 2.0x10–6 mol/L of dosage was reached under the conditions of dioxygen pressure of 2.5 MPa at 150°C for 4 h.This was the best result reported for this reaction up to now.The QSAR models for each concerned metallopor-phyrin were established,where the catalytic activity was significantly correlated with the ELUMO(the energy level of the lowest unoccupied molecule orbit)and LM-N(the bond length between metal-nitrogen atoms).Using the QSAR models,four new metalloporphyrins with substituted nitro group were designed,and their catalytic activities were predicted.The experimental TON data of newly designed porphyrins were in good agreement with the predicted ones,and the square of their correlation coefficient was more than 0.958.The above results demonstrated that the proposed structure-activity relationship model could be applied to design some new metalloporphyrin catalysts,and to predict their catalytic activity in cyclohexane oxidation.展开更多
基金the National Science Fund for Distinguished Young Scholars(No.51625801)the Guangdong Innovation Team Project for Colleges and Universities(No.2016KCXTD023)+1 种基金Guangdong Province Universities andColleges Pearl River Scholar Funded Scheme(2017)the China Postdoctoral Science Foundation(No.2018M643671)。
文摘Electrochemical degradation of sulfamethoxazole(SMX)and its metabolite acetyl-sulfamethoxazole(AcSMX)by Ti/SnO_(2)-Sb/Er-PbO_(2) were investigated.Results indicated that the electrochemical degradation of SMX and Ac-SMX followed pseudo-first-order kinetics.The rate constants of SMX and Ac-SMX were 0.268 and 0.072 min-1 at optimal curre nt density of 10 and 14 mA/cm^(2),respectively.Transformation products of SMX and Ac-SMX were identified and the possible degradation pathways,including the cleavage of S-N bond,opening ring of isoxazole and nitration of amino group,were proposed.Total organic carbon removal of SMX was nearly 63.2%after 3 h electrochemical degradation.22.4%nitrogen of SMX was trans formed to NO_(3)-,and 98.8%sulfur of SMX was released as SO_(4)2-.According to quantitative structureactivity relationship model,toxicities of SMX and Ac-SMX to aquatic organisms significantly decreased after electrochemical degradation.Electric energy consumption for 90%SMX and Ac-SMX degradation was determined to be 0.58-8.97 and 6.88-44.19 Wh/L at different experimental conditions,respectively.Compared with parent compound SMX,the metabolite Ac-SMX is more refractory and toxic,which emphasizes the importance of taking its metabolites into account when investigating the disposal of pharmaceuticals from wastewater.
基金Project supported by the National Natural Science Foundation of China.
文摘The artificial neural network (ANN) model with back-propagation of error is used to study the quantitative structure-activity relationship of para-substituted phenol derivatives between the biological activity and the physicochemical property parameters. Network parameters are optimized, and an empirical rule for dynamically adjusting the network’s learning rate is proposed to improve the network’s performance. The results showthat the three-layer ANN model gives satisfactory performance, with f(x)=1/(1+exp(-x)) as the network node’s input-output transformation function and the number of hidden nodes 10. The network gives the mean square error (rose) of 0.036 when predicting the biological activity of 26 para-substituted phenol derivatives. This result compares favourably with that obtained by the conventional methods.
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.
文摘An old drug with a new use can significantly reduce the cost and time for new drug research and development. MAPK （Mitogen-activated protein kinase） plays a very important key role in signal transduction pathways of cell proliferation and differentiation. According to the statistics, there are about 30% persons who suffered from cancers related to the MAPK signal transduction pathways. Therefore, many researchers are focused on blocking these pathways in cancers therapies. Ras/Raf/MEK/ERK, however, is one of very important pathways among MAPK message transduction pathways. More and more information about MEK protein inhibitors are unveiled in several recent years. In the present study, the authors utilized MEK inhibitors which were already published and their activities were available to construct 2D-QSAR model by using CADD （multiple linear regression）. Then, the authors searched certified FDA drugs （Drugs@FDA 6184 drugs） making preliminary screening. The secondary screening on 3D structures were followed by using Docking, Scoring and Pharmacophore analysis to find out most suitable MEK inhibitors to become a fundamental database in drug discovery. The results are shown the ALogP, number of aromatic rings, number of hydrogen bond acceptors and number of hydrogen bond donors are all in positive correlation. According to the equation from 2D-QSAR model, the results conform to the previous description.
基金supported by the Key Project of Natural Science Foundation of Beijing(Grant No.2061001).
文摘The catalysis of chloridized metalloporphyrins in the oxidation of cyclohexane to adipic acid was systemati-cally investigated.The turnover numbers(TON)data of 19 catalysts were obtained experimentally under optimal reac-tion conditions,and 2.4x106 TON for T(o-Cl)PP-MnIIICl catalyst at 2.0x10–6 mol/L of dosage was reached under the conditions of dioxygen pressure of 2.5 MPa at 150°C for 4 h.This was the best result reported for this reaction up to now.The QSAR models for each concerned metallopor-phyrin were established,where the catalytic activity was significantly correlated with the ELUMO(the energy level of the lowest unoccupied molecule orbit)and LM-N(the bond length between metal-nitrogen atoms).Using the QSAR models,four new metalloporphyrins with substituted nitro group were designed,and their catalytic activities were predicted.The experimental TON data of newly designed porphyrins were in good agreement with the predicted ones,and the square of their correlation coefficient was more than 0.958.The above results demonstrated that the proposed structure-activity relationship model could be applied to design some new metalloporphyrin catalysts,and to predict their catalytic activity in cyclohexane oxidation.
