目的计算药物溶出度W e ibu ll分布参数。方法采用SAS软件非线性回归NLIN程序包中的Levenberg-M arquardt法进行迭代计算。结果本方法计算的结果与文献的记录相吻合。结论本方法简便、快速、拟合结果准确,适用于药学工作者对药物溶出度W...目的计算药物溶出度W e ibu ll分布参数。方法采用SAS软件非线性回归NLIN程序包中的Levenberg-M arquardt法进行迭代计算。结果本方法计算的结果与文献的记录相吻合。结论本方法简便、快速、拟合结果准确,适用于药学工作者对药物溶出度W e ibu ll分布的计算。展开更多
Plasmodium falciparum(P.falciparum) is responsible for the majority of life-threatening cases of human malaria,causing 1.5-2.7 million annual deaths.The global emergence of drug-resistant malaria parasites necessitate...Plasmodium falciparum(P.falciparum) is responsible for the majority of life-threatening cases of human malaria,causing 1.5-2.7 million annual deaths.The global emergence of drug-resistant malaria parasites necessitates identification and characterisation of novel drug targets and their potential inhibitors.We identified the carbonic anhydrase(CA) genes in P.falciparum.The pfGA gene encodes an α-carbonic anhydrase,a Zn^(2+)-metalloenzme,possessing catalytic properties distinct from that of the human host CA enzyme.The amino acid sequence of the pfCA enzyme is different from the analogous protozoan and human enzymes.A library of aromatic/heterocyclic sulfonamides possessing a large diversity of scaffolds were found to be very good inhibitors for the malarial enzyme at moderate-low micromolar and submicromolar inhibitions.The structure of the groups substituting the aromatic-ureido-or aromatic-azomethine fragment of the molecule and the length of the parent sulfonamide were critical parameters for the inhibitory properties of the sulfonamides.One derivative,that is,4-(3,4-dichlorophenylureido)thioureidobcnzcnesulfonamide(compound 10) was the most effective in vitro Plasmodium falciparum CA inhibitor,and was also the most effective antimalarial compound on the in vitro P.falciparum growth inhibition.The compound 10 was also effective in vivo antimalarial agent in mice infected with Plasmodium berghei,an animal model of drug testing for human malaria infection. It is therefore concluded that the sulphonamide inhibitors targeting the parasite CA may have potential for the development of novel therapies against human malaria.展开更多
Modification of sulfonamid drug using different principles of chemical reactions was investigated. These reactions involve the condensation of an amino group with triethyl orthoformate and dimethylformamide dimethyl a...Modification of sulfonamid drug using different principles of chemical reactions was investigated. These reactions involve the condensation of an amino group with triethyl orthoformate and dimethylformamide dimethyl acetal. Ability of sulfa to condense with active keto compounds, like ethyl pyruvate and piprazine carboxyaldehye was studied. Alkyation of sulfa with different chloro derivatives was also reported. The structure of the isolated compound was elucidated and confirmed using elemental analysis and spectral data. The bioactivity of the ob-tained compounds was investigated against different gram positive and gram negative bacteria. The study reveals that most of the modified drugs show high to moderate antibacterial activity.展开更多
本研究建立了基于超高效液相色谱串联质谱技术(Ultra Performance Liquid Chromatography Tandem Mass Spectrometry,UPLC-MS/MS)的磺胺类兽药残留分析方法。方法学考察表明,11种磺胺类兽药残留在10~200μg·L^(-1)呈现良好的线性关...本研究建立了基于超高效液相色谱串联质谱技术(Ultra Performance Liquid Chromatography Tandem Mass Spectrometry,UPLC-MS/MS)的磺胺类兽药残留分析方法。方法学考察表明,11种磺胺类兽药残留在10~200μg·L^(-1)呈现良好的线性关系;方法检出限为0.84~1.62μg·kg^(-1),方法定量限为2.8~5.4μg·kg^(-1);在3个浓度水平下,目标化合物的加标回收率为74.5%~109.9%,相对标准偏差为0.09%~8.12%。该方法可用于动物源食品中多种磺胺类兽药残留的定性、定量分析及筛查。展开更多
基金Supported by a grant from UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases(No.900142,930143,960103,970074,990490)the National Science and Technology Development Agency of Thailand(Career Development Award ID no.01-38-007)the Thailand Research Fund(BasicResearch Grants ID No.BRG/13/2543.BRG4580020.BRG 4880006)
文摘Plasmodium falciparum(P.falciparum) is responsible for the majority of life-threatening cases of human malaria,causing 1.5-2.7 million annual deaths.The global emergence of drug-resistant malaria parasites necessitates identification and characterisation of novel drug targets and their potential inhibitors.We identified the carbonic anhydrase(CA) genes in P.falciparum.The pfGA gene encodes an α-carbonic anhydrase,a Zn^(2+)-metalloenzme,possessing catalytic properties distinct from that of the human host CA enzyme.The amino acid sequence of the pfCA enzyme is different from the analogous protozoan and human enzymes.A library of aromatic/heterocyclic sulfonamides possessing a large diversity of scaffolds were found to be very good inhibitors for the malarial enzyme at moderate-low micromolar and submicromolar inhibitions.The structure of the groups substituting the aromatic-ureido-or aromatic-azomethine fragment of the molecule and the length of the parent sulfonamide were critical parameters for the inhibitory properties of the sulfonamides.One derivative,that is,4-(3,4-dichlorophenylureido)thioureidobcnzcnesulfonamide(compound 10) was the most effective in vitro Plasmodium falciparum CA inhibitor,and was also the most effective antimalarial compound on the in vitro P.falciparum growth inhibition.The compound 10 was also effective in vivo antimalarial agent in mice infected with Plasmodium berghei,an animal model of drug testing for human malaria infection. It is therefore concluded that the sulphonamide inhibitors targeting the parasite CA may have potential for the development of novel therapies against human malaria.
文摘Modification of sulfonamid drug using different principles of chemical reactions was investigated. These reactions involve the condensation of an amino group with triethyl orthoformate and dimethylformamide dimethyl acetal. Ability of sulfa to condense with active keto compounds, like ethyl pyruvate and piprazine carboxyaldehye was studied. Alkyation of sulfa with different chloro derivatives was also reported. The structure of the isolated compound was elucidated and confirmed using elemental analysis and spectral data. The bioactivity of the ob-tained compounds was investigated against different gram positive and gram negative bacteria. The study reveals that most of the modified drugs show high to moderate antibacterial activity.
文摘本研究建立了基于超高效液相色谱串联质谱技术(Ultra Performance Liquid Chromatography Tandem Mass Spectrometry,UPLC-MS/MS)的磺胺类兽药残留分析方法。方法学考察表明,11种磺胺类兽药残留在10~200μg·L^(-1)呈现良好的线性关系;方法检出限为0.84~1.62μg·kg^(-1),方法定量限为2.8~5.4μg·kg^(-1);在3个浓度水平下,目标化合物的加标回收率为74.5%~109.9%,相对标准偏差为0.09%~8.12%。该方法可用于动物源食品中多种磺胺类兽药残留的定性、定量分析及筛查。
