A three-dimensional quantitative structure-activity relationship （3D-QSAR） study of a series of 7,8-dialkyl-l,3-diaminopyrrolo-[3,2-f] quinazolines with anticancer activity as dihydrofo- late reductase （DHFR） inhi...A three-dimensional quantitative structure-activity relationship （3D-QSAR） study of a series of 7,8-dialkyl-l,3-diaminopyrrolo-[3,2-f] quinazolines with anticancer activity as dihydrofo- late reductase （DHFR） inhibitors was carried out by using the comparative molecular field analysis （CoMFA）, on the basis of our reported 2D-QSAR of these compounds. The es- tablished 3D-QSAR model has good quality of statistics and good prediction ability; the non cross-validation correlation coefficient and the cross-validation value of this model are 0.993 and 0.619, respectively, the F value is 193.4, and the standard deviation SD is 0.208. This model indicates that the steric field factor plays a much more important role than the electrostatic one, in satisfying agreement with the published 2D-QSAR model. However, the 3D-QSAR model offers visual images of the steric field and the electrostatic field. The 3D-QSAR study further suggests the following： to improve the activity, the substituent R^1 should be selected to be a group with an adaptive bulk like Et or i-Pr, and the substituent R should be selected to be a larger alkyl. In particular, based on our present 3D-QSAR as well as the published 2D-QSAR, the experimentMly-proposed hydrophobic binding mechanism on the receptor-binding site of the DHFR can be further explained in theory. Therefore, the QSAR studies help to further understand the ＂hydrophobic binding＂ action mechanism of this kind of compounds, and to direct the molecular design of new drugs with higher activity.展开更多
探究秦川牛宰后成熟过程中线粒体Tu翻译延长因子(mitochondrial Tu translation elongation factor,TUFM)表达对肉的持水性影响。以秦川牛背最长肌为研究对象,测定4℃不同成熟时间下的pH值、贮藏损失、离心损失、蒸煮损失、水分分布、...探究秦川牛宰后成熟过程中线粒体Tu翻译延长因子(mitochondrial Tu translation elongation factor,TUFM)表达对肉的持水性影响。以秦川牛背最长肌为研究对象,测定4℃不同成熟时间下的pH值、贮藏损失、离心损失、蒸煮损失、水分分布、肌原纤维蛋白等指标变化情况,测定不同成熟时间(0、96、192 h)下TUFM表达量及其含量、Beclin1蛋白表达量。结果显示:在秦川牛宰后成熟期间,肌原纤维蛋白发生降解,TUFM的表达量与Beclin1蛋白表达量和牛肉的持水性存在密切关系,其中蛋白质组学测定的TUFM表达量变化与TUFM含量变化趋势一致,Beclin1蛋白表达量、贮藏损失、离心损失、蒸煮损失整体均呈先上升后下降趋势,pH值呈先下降后上升趋势;Pearson相关性分析表明,牛背最长肌中TUFM表达量与低场核磁共振峰面积比P_(2b)、Beclin1蛋白表达量呈极显著正相关(P<0.01),与贮藏损失、离心损失、蒸煮损失呈显著正相关(P<0.05),与P_(21)呈极显著负相关(P<0.01),与P_(22)呈显著负相关(P<0.05),与pH值无显著相关性(P>0.05)。通过蛋白质组学鉴定出23种与TUFM相关的差异蛋白,通过基因本体论、京都基因与基因组百科全书通路分析发现,差异蛋白可通过多种途径参与能量代谢,进而介导细胞自噬;对差异蛋白和持水性指标进行Pearson相关性分析发现,有5种差异蛋白(ATP5F1D、EEF1A2、GSPT1、NDUFB5、SUCLG1)与持水性指标具有显著相关性(P<0.05、P<0.01)。分析可知,包括TUFM在内,共6种蛋白主要通过能量代谢和氧转运等途径正向或负向影响细胞自噬,从而影响肉的持水性。展开更多
In silico pharmacokinetics studies can aid the search for molecules with potential ability to be drug candidates. In this paper, a number of quinazoline candidates for epidermal growth factor receptor inhibitors—EGFR...In silico pharmacokinetics studies can aid the search for molecules with potential ability to be drug candidates. In this paper, a number of quinazoline candidates for epidermal growth factor receptor inhibitors—EGFR, important targets for the treatment of cancer, are computationally analyzed. The literature described that 69 quinazoline molecules were synthesized and the respective half maximum inhibitory concentrations (IC50) were obtained. A bilinear parabolic model was built to investigate the druglikeness by correlating the corresponding lipophilicities, which can be represented by the ideal Log P , with the optimal biological activity in terms of pIC50 values. Structural characteristics leading to improved pharmacokinetics parameters were then analyzed. Compound 56 exhibited the lowest IC50 and, therefore, it had the highest ability to inhibit the EGFR. In the present work, the most potent inhibitor 56 is not calculated to be the most promising drug candidate, since it’s out of the parabolic model obtained due to a Log P above 5, which is not within the expected optimum range. Finally, this work is an example of computational prediction that an experimentally, highly active EGFR inhibitor can be unsuccessful as drug candidate because of pitfalls in pharmacokinetics parameters.展开更多
Objective: To synthesize inhibitors of the epidermal growth factor receptor tyrosine kinase such as 6-nitro-4-anilinoquinazolines and 6-amino-4-anilinoquinazolines,and to compare their anticancer effects in vitro. Met...Objective: To synthesize inhibitors of the epidermal growth factor receptor tyrosine kinase such as 6-nitro-4-anilinoquinazolines and 6-amino-4-anilinoquinazolines,and to compare their anticancer effects in vitro. Methods: The 4-anilinoquinazolines compounds were prepared by hydrolyzed, ringed, halagenated, substituded in turn from 2-amino-5-nitrobenzylcarbonitril. The synthesized 4- anilinoquinazoline compounds has been rudimentarily screened by using A431 tumor cell line which overexpresses epidermal growth factor receptor as model adopted MTT method. Results: Five 6-nitro-4-halo-sbstituted anilinoquinazolines and five 6-amino-4-halo-substituted anilinoquinazolines have been obtained,and all of them had anticancer activity. The anticancer activity of 6-amino substituted inhibitors was higher than that of 6-nitro substituted inhibitors. However, the difference of anticancer activity between two series of quinazoline was much less than that of their inhibiting EGFR tyrosine kinase activity. Conclusion: The probable reason for 6-nitro-4-anilinoquinazolines having anticancer activity in vitro was that they had been partially transformed to 6-amino-4-anilinoquinazolines through endocellular cytochrome oxidation-reduction system.展开更多
The title compound, 2,6-bis（benzimidazo（1,2-c）quinazolin-6-yl）pyridine tetrahydrate, was synthesized by simple condensation of 2-（2-sminophenyl） benzimidazole with pyfidine- 2,6-dicarboxylic acid and characteriz...The title compound, 2,6-bis（benzimidazo（1,2-c）quinazolin-6-yl）pyridine tetrahydrate, was synthesized by simple condensation of 2-（2-sminophenyl） benzimidazole with pyfidine- 2,6-dicarboxylic acid and characterized by elemental analysis, IR spectra and single-crystal X-ray diffraction. The crystal belongs to the monoclinic system, space group C2/c with a = 22.226（8）, b = 16.730（7）, c = 16.820（5）A, β = 115.796（13）°, V = 5631（4）A^3, C33H27NTO4, Mr = 585.62, Z = 8, Dc = 1.381 g/cm^3, λ（MoKα） = 0.71073 A, F（000） = 2448 and μ = 0.09 mm^-1. The structure was refined to the final R = 0.0730 and wR = 0.1573 for 6346 independent reflections （Rint = 0.0801） and 3384 observed reflections （I 〉 2σ（I））. In the crystal, the molecules are linked through intermolecular O-H…O and O-H…N hydrogen bonds. Intermolecular π-π interactions （with distances of about 3.45 A） are pronounced in the crystal structure.展开更多
As a group of diversified frameworks, quinazolin derivatives displayed a broad field of biological functions, especially as anticancer. To investigate the quantitative structure-activity relationship, 3D-QSAR models ...As a group of diversified frameworks, quinazolin derivatives displayed a broad field of biological functions, especially as anticancer. To investigate the quantitative structure-activity relationship, 3D-QSAR models were generated with 24 quinazolin scaffold molecules. The experimental and predicted pIC50 values for both training and test set compounds showed good correlation, which proved the robustness and reliability of the generated QSAR models. The most effective CoMFA and CoMSIA were obtained with correlation coefficient2ncv r of 1.00 （both） and leave-one-out coefficient q2 of 0.61 and 0.59, respectively. The predictive abilities of CoMFA and CoMSIA were quite good with the predictive correlation coefficients （2pred r ） of 0.97 and 0.91. In addition, the statis-tic results of CoMFA and CoMSIA were used to design new quinazolin molecules.展开更多
Objective:To study the anti-ovarian cancer effect and mechanism of Quinazoline derivative(N111)in vitro;Method:Using an online database to predict the therapeutic targets of N111 for ovarian cancer,and conducting biol...Objective:To study the anti-ovarian cancer effect and mechanism of Quinazoline derivative(N111)in vitro;Method:Using an online database to predict the therapeutic targets of N111 for ovarian cancer,and conducting biological functional analysis of the therapeutic targets.The experiment was divided into N111 treatment group(N111 compound group),positive control group(cisplatin group),and negative control group(DMSO group);After grouping,MTT assay was used to detect cell proliferation;Morphological observation was used to observe changes in cell morphology;JC-1 and DCFH-DA probes were used to detect the changes of mitochondrial Membrane potential and intracellular reactive oxygen species;PI,Annexin V-FITC,and DAPI staining were used to detect cell cycle arrest and apoptosis;Clone formation experiments and scratch tests were conducted to detect the cell's ability to form clones and migrate;Western blot method was used to detect the expression level of related proteins.Result:The biological function research results show that the biological function of N111 anti ovarian cancer target protein suggests that the target function aggregates human diseases,inflammation,tumors,and other aspects.Compared with the control group,N111 has a significant inhibitory effect on the proliferation of ovarian cancer cells(IC50=14.62 mmol/L)(P<0.0001);In a concentration dependent manner,it inhibited the formation and migration of single cell colonies,and induced the disorder of mitochondrial Membrane potential,ROS and cell cycle arrest in S phase(P<0.0001);As the concentration of N111 treatment increased,the expression levels of Bcl2,Caspase 3,P-AKT,and SHIP2 decreased,while the expression levels of AKT remained unchanged.The expression levels of Bax and Cleared Caspase 3 increased(P<0.0001).Conclusion:Compound N111 inhibits SHIP2,promotes ROS level disorder,weakens the activation of AKT signaling pathway,and thus inhibits the proliferation,migration,and clone formation of tumor cell A2780,inducing cell apoptosis.展开更多
Jiu Ai Tu(The Moxa Treatment)from the Song dynasty is the earliest surviving painting that focuses on the subject of acupuncture and moxibustion.This paper takes the medical activities depicted in the artwork as its r...Jiu Ai Tu(The Moxa Treatment)from the Song dynasty is the earliest surviving painting that focuses on the subject of acupuncture and moxibustion.This paper takes the medical activities depicted in the artwork as its research object and systematically analyzes the external treatment methods for abscesses during the Song dynasty reflected in Jiu Ai Tu.By examining the understanding of abscesses during that period,the paper explores the level of development in external medicine techniques.By analyzing the medical awareness and behaviors of patients when facing such severe illnesses,it aims to explore the societal cognition and experiences regarding health and disease.The paper attempts to present the folk medical ecology of the Song dynasty represented by Jiu Ai Tu.展开更多
The title compound 3,3＇-（2,2＇-（ethane-1,2-diylbis（oxy））bis（ethane-2,1-diyl））bis（2- （4-chlorophenylamino）quinazolin-4（3H）-one） 3 （C34H30CI2N604, Mr = 657.54） has been synthesized and its crystal struc...The title compound 3,3＇-（2,2＇-（ethane-1,2-diylbis（oxy））bis（ethane-2,1-diyl））bis（2- （4-chlorophenylamino）quinazolin-4（3H）-one） 3 （C34H30CI2N604, Mr = 657.54） has been synthesized and its crystal structure was determined by single-crystal X-ray diffraction analysis. It crystallizes in space group P1 with a = 9.9185（8）, b = 10.6124（9）, c = 15.4064（13） A, α = 92.896（2）,β = 103.813（2）, γ= 94.635（2）°, V= 1565.5（2） A3, Z = 2, Dc = 1.395 g/cm^3,μ = 0.257 mm^-1, F（000） = 684, the final R = 0.0580 and wR = 0.1284 for 3400 observed reflections （I〉 2σ（I）. It remains triclinic in the crystal. Intra- and intermolecular N（3）-H（3A）…O（2）, N（6）-H（6A）…O（3） and C（19）-H（19A）…O（4） #1 （#1： 1-x, 1-y, -z） hydrogen bonds are observed in the title compound. A two-dimensional chain network is formed from the dimmers and intermolecular π-π interactions in the crystal structure. This open network has solvent-accessible voids （10A3）.展开更多
Objective:To determine the active components of Eupolyphaga sinensis Walker(Tu Bie Chong)and explore the mechanisms underlying its fracture-healing ability.Methods: A modified Einhorn method was used to develop a rat ...Objective:To determine the active components of Eupolyphaga sinensis Walker(Tu Bie Chong)and explore the mechanisms underlying its fracture-healing ability.Methods: A modified Einhorn method was used to develop a rat tibial fracture model.Progression of bone healing was assessed using radiological methods.Safranin O/fast green and CD31 immunohistochemical staining were performed to evaluate the growth of bone cells and angiogenesis at the fracture site.Methylthiazoletetrazolium blue and wound healing assays were used to analyze cell viability and migration.The Transwell assay was used to explore the invasion capacity of the cells.Tubule formation assays were used to assess the angiogenesis capacity of human vascular endothelial cells(HUVECs).qRT-PCR was used to evaluate the changes in gene transcription levels.Results: Tu Bie Chong fraction 3(TF3)significantly shortened the fracture healing time in model rats.X-ray results showed that on day 14,fracture healing in the TF3 treatment group was significantly better than that in the control group(P=.0086).Tissue staining showed that cartilage growth and the number of H-shaped blood vessels at the fracture site of the TF3 treatment group were better than those of the control group.In vitro,TF3 significantly promoted the proliferation and wound healing of MC3T3-E1s and HUVECs(all P<.01).Transwell assays showed that TF3 promoted the migration of HUVECs,but inhibited the migration of MC3T3-E1 cells.Tubule formation experiments confirmed that TF3 markedly promoted the ability of vascular endothelial cells to form microtubules.Gene expression analysis revealed that TF3 significantly promoted the expression of VEGFA,SPOCD1,NGF,and NGFR in HUVECs.In MC3T3-E1 cells,the transcript levels of RUNX2 and COL2A1 were significantly elevated following TF3 treatment.Conclusion: TF3 promotes fracture healing by promoting bone regeneration associated with the RUNX2 pathway and angiogenesis associated with the VEGFA pathway.展开更多
Geometry optimization and subsequent harmonic vibration calculations of prior synthesized （E）-3-（4-fluorophenyl）-N-[4-（phenyl-amino） quinazoline-7-yl] acrylamide were carried out by DFT/B3LYP method with both 6-...Geometry optimization and subsequent harmonic vibration calculations of prior synthesized （E）-3-（4-fluorophenyl）-N-[4-（phenyl-amino） quinazoline-7-yl] acrylamide were carried out by DFT/B3LYP method with both 6-31G and 6-311G basis sets.The Infrared （IR） spectrum of the title compound was recorded in the field of 400-4000 cm 1 and then assigned.The correlation analyses between the scaled theoretical vibration frequencies and the experimental ones indicate that there exist good linearity relationships since the correlation coefficients R 2 are larger than 0.999.The intramolecular interactions existed in the title molecule were confirmed by the Atoms in molecules （AIM） method,and their influences on the absorption frequency were also investigated.展开更多
基金This work was supported by the National Natural Science Foundation of China （No.20673148）. We also heartily thank the College of Life Sciences, Sun Yat-Sen University for the SYBYL 6.9 computation environment support.
文摘A three-dimensional quantitative structure-activity relationship （3D-QSAR） study of a series of 7,8-dialkyl-l,3-diaminopyrrolo-[3,2-f] quinazolines with anticancer activity as dihydrofo- late reductase （DHFR） inhibitors was carried out by using the comparative molecular field analysis （CoMFA）, on the basis of our reported 2D-QSAR of these compounds. The es- tablished 3D-QSAR model has good quality of statistics and good prediction ability; the non cross-validation correlation coefficient and the cross-validation value of this model are 0.993 and 0.619, respectively, the F value is 193.4, and the standard deviation SD is 0.208. This model indicates that the steric field factor plays a much more important role than the electrostatic one, in satisfying agreement with the published 2D-QSAR model. However, the 3D-QSAR model offers visual images of the steric field and the electrostatic field. The 3D-QSAR study further suggests the following： to improve the activity, the substituent R^1 should be selected to be a group with an adaptive bulk like Et or i-Pr, and the substituent R should be selected to be a larger alkyl. In particular, based on our present 3D-QSAR as well as the published 2D-QSAR, the experimentMly-proposed hydrophobic binding mechanism on the receptor-binding site of the DHFR can be further explained in theory. Therefore, the QSAR studies help to further understand the ＂hydrophobic binding＂ action mechanism of this kind of compounds, and to direct the molecular design of new drugs with higher activity.
基金The authors are thankful to Program to Support Publishing(PROPESQ)of Federal University of Juiz de Fora—UFJF and FAPEMIG.
文摘In silico pharmacokinetics studies can aid the search for molecules with potential ability to be drug candidates. In this paper, a number of quinazoline candidates for epidermal growth factor receptor inhibitors—EGFR, important targets for the treatment of cancer, are computationally analyzed. The literature described that 69 quinazoline molecules were synthesized and the respective half maximum inhibitory concentrations (IC50) were obtained. A bilinear parabolic model was built to investigate the druglikeness by correlating the corresponding lipophilicities, which can be represented by the ideal Log P , with the optimal biological activity in terms of pIC50 values. Structural characteristics leading to improved pharmacokinetics parameters were then analyzed. Compound 56 exhibited the lowest IC50 and, therefore, it had the highest ability to inhibit the EGFR. In the present work, the most potent inhibitor 56 is not calculated to be the most promising drug candidate, since it’s out of the parabolic model obtained due to a Log P above 5, which is not within the expected optimum range. Finally, this work is an example of computational prediction that an experimentally, highly active EGFR inhibitor can be unsuccessful as drug candidate because of pitfalls in pharmacokinetics parameters.
文摘Objective: To synthesize inhibitors of the epidermal growth factor receptor tyrosine kinase such as 6-nitro-4-anilinoquinazolines and 6-amino-4-anilinoquinazolines,and to compare their anticancer effects in vitro. Methods: The 4-anilinoquinazolines compounds were prepared by hydrolyzed, ringed, halagenated, substituded in turn from 2-amino-5-nitrobenzylcarbonitril. The synthesized 4- anilinoquinazoline compounds has been rudimentarily screened by using A431 tumor cell line which overexpresses epidermal growth factor receptor as model adopted MTT method. Results: Five 6-nitro-4-halo-sbstituted anilinoquinazolines and five 6-amino-4-halo-substituted anilinoquinazolines have been obtained,and all of them had anticancer activity. The anticancer activity of 6-amino substituted inhibitors was higher than that of 6-nitro substituted inhibitors. However, the difference of anticancer activity between two series of quinazoline was much less than that of their inhibiting EGFR tyrosine kinase activity. Conclusion: The probable reason for 6-nitro-4-anilinoquinazolines having anticancer activity in vitro was that they had been partially transformed to 6-amino-4-anilinoquinazolines through endocellular cytochrome oxidation-reduction system.
基金supported by the Natural Science Foundation of Fujian Province (2007J0216, U0750004)the Ministry of Education of China (No. 208066)+1 种基金the Education Department of Fujian Province (JA07029)the State Key Laboratory of Structural Chemistry (No. 20080053)
文摘The title compound, 2,6-bis（benzimidazo（1,2-c）quinazolin-6-yl）pyridine tetrahydrate, was synthesized by simple condensation of 2-（2-sminophenyl） benzimidazole with pyfidine- 2,6-dicarboxylic acid and characterized by elemental analysis, IR spectra and single-crystal X-ray diffraction. The crystal belongs to the monoclinic system, space group C2/c with a = 22.226（8）, b = 16.730（7）, c = 16.820（5）A, β = 115.796（13）°, V = 5631（4）A^3, C33H27NTO4, Mr = 585.62, Z = 8, Dc = 1.381 g/cm^3, λ（MoKα） = 0.71073 A, F（000） = 2448 and μ = 0.09 mm^-1. The structure was refined to the final R = 0.0730 and wR = 0.1573 for 6346 independent reflections （Rint = 0.0801） and 3384 observed reflections （I 〉 2σ（I））. In the crystal, the molecules are linked through intermolecular O-H…O and O-H…N hydrogen bonds. Intermolecular π-π interactions （with distances of about 3.45 A） are pronounced in the crystal structure.
基金financial supports from the National Natural Science Foundation of China (Nos. 50673085, 20677053)the National High-Tech Research and Development Programme of China (No. 2010AA09Z203)
文摘As a group of diversified frameworks, quinazolin derivatives displayed a broad field of biological functions, especially as anticancer. To investigate the quantitative structure-activity relationship, 3D-QSAR models were generated with 24 quinazolin scaffold molecules. The experimental and predicted pIC50 values for both training and test set compounds showed good correlation, which proved the robustness and reliability of the generated QSAR models. The most effective CoMFA and CoMSIA were obtained with correlation coefficient2ncv r of 1.00 （both） and leave-one-out coefficient q2 of 0.61 and 0.59, respectively. The predictive abilities of CoMFA and CoMSIA were quite good with the predictive correlation coefficients （2pred r ） of 0.97 and 0.91. In addition, the statis-tic results of CoMFA and CoMSIA were used to design new quinazolin molecules.
基金Anhui Province University Natural Science Research Project (No.KJ2019A0363)。
文摘Objective:To study the anti-ovarian cancer effect and mechanism of Quinazoline derivative(N111)in vitro;Method:Using an online database to predict the therapeutic targets of N111 for ovarian cancer,and conducting biological functional analysis of the therapeutic targets.The experiment was divided into N111 treatment group(N111 compound group),positive control group(cisplatin group),and negative control group(DMSO group);After grouping,MTT assay was used to detect cell proliferation;Morphological observation was used to observe changes in cell morphology;JC-1 and DCFH-DA probes were used to detect the changes of mitochondrial Membrane potential and intracellular reactive oxygen species;PI,Annexin V-FITC,and DAPI staining were used to detect cell cycle arrest and apoptosis;Clone formation experiments and scratch tests were conducted to detect the cell's ability to form clones and migrate;Western blot method was used to detect the expression level of related proteins.Result:The biological function research results show that the biological function of N111 anti ovarian cancer target protein suggests that the target function aggregates human diseases,inflammation,tumors,and other aspects.Compared with the control group,N111 has a significant inhibitory effect on the proliferation of ovarian cancer cells(IC50=14.62 mmol/L)(P<0.0001);In a concentration dependent manner,it inhibited the formation and migration of single cell colonies,and induced the disorder of mitochondrial Membrane potential,ROS and cell cycle arrest in S phase(P<0.0001);As the concentration of N111 treatment increased,the expression levels of Bcl2,Caspase 3,P-AKT,and SHIP2 decreased,while the expression levels of AKT remained unchanged.The expression levels of Bax and Cleared Caspase 3 increased(P<0.0001).Conclusion:Compound N111 inhibits SHIP2,promotes ROS level disorder,weakens the activation of AKT signaling pathway,and thus inhibits the proliferation,migration,and clone formation of tumor cell A2780,inducing cell apoptosis.
基金financed from the grant of the National Social Science Foundation General Project(No.23BZS010)。
文摘Jiu Ai Tu(The Moxa Treatment)from the Song dynasty is the earliest surviving painting that focuses on the subject of acupuncture and moxibustion.This paper takes the medical activities depicted in the artwork as its research object and systematically analyzes the external treatment methods for abscesses during the Song dynasty reflected in Jiu Ai Tu.By examining the understanding of abscesses during that period,the paper explores the level of development in external medicine techniques.By analyzing the medical awareness and behaviors of patients when facing such severe illnesses,it aims to explore the societal cognition and experiences regarding health and disease.The paper attempts to present the folk medical ecology of the Song dynasty represented by Jiu Ai Tu.
基金supported by the Open Fund of Ministry-of-education Key Laboratory for the Synthesis and Application of Organic Functional Molecules (No. 2006-KL-013)
文摘The title compound 3,3＇-（2,2＇-（ethane-1,2-diylbis（oxy））bis（ethane-2,1-diyl））bis（2- （4-chlorophenylamino）quinazolin-4（3H）-one） 3 （C34H30CI2N604, Mr = 657.54） has been synthesized and its crystal structure was determined by single-crystal X-ray diffraction analysis. It crystallizes in space group P1 with a = 9.9185（8）, b = 10.6124（9）, c = 15.4064（13） A, α = 92.896（2）,β = 103.813（2）, γ= 94.635（2）°, V= 1565.5（2） A3, Z = 2, Dc = 1.395 g/cm^3,μ = 0.257 mm^-1, F（000） = 684, the final R = 0.0580 and wR = 0.1284 for 3400 observed reflections （I〉 2σ（I）. It remains triclinic in the crystal. Intra- and intermolecular N（3）-H（3A）…O（2）, N（6）-H（6A）…O（3） and C（19）-H（19A）…O（4） #1 （#1： 1-x, 1-y, -z） hydrogen bonds are observed in the title compound. A two-dimensional chain network is formed from the dimmers and intermolecular π-π interactions in the crystal structure. This open network has solvent-accessible voids （10A3）.
基金supported by“the Fundamental Research Funds for the Central Universities”(2020-JYB-ZDGG-054)“Beijing university of Chinese medicine XINAO Award Fund”(2019)Beijing University of Chinese Medicine Scientific Research and Development Fund(2170072220002).
文摘Objective:To determine the active components of Eupolyphaga sinensis Walker(Tu Bie Chong)and explore the mechanisms underlying its fracture-healing ability.Methods: A modified Einhorn method was used to develop a rat tibial fracture model.Progression of bone healing was assessed using radiological methods.Safranin O/fast green and CD31 immunohistochemical staining were performed to evaluate the growth of bone cells and angiogenesis at the fracture site.Methylthiazoletetrazolium blue and wound healing assays were used to analyze cell viability and migration.The Transwell assay was used to explore the invasion capacity of the cells.Tubule formation assays were used to assess the angiogenesis capacity of human vascular endothelial cells(HUVECs).qRT-PCR was used to evaluate the changes in gene transcription levels.Results: Tu Bie Chong fraction 3(TF3)significantly shortened the fracture healing time in model rats.X-ray results showed that on day 14,fracture healing in the TF3 treatment group was significantly better than that in the control group(P=.0086).Tissue staining showed that cartilage growth and the number of H-shaped blood vessels at the fracture site of the TF3 treatment group were better than those of the control group.In vitro,TF3 significantly promoted the proliferation and wound healing of MC3T3-E1s and HUVECs(all P<.01).Transwell assays showed that TF3 promoted the migration of HUVECs,but inhibited the migration of MC3T3-E1 cells.Tubule formation experiments confirmed that TF3 markedly promoted the ability of vascular endothelial cells to form microtubules.Gene expression analysis revealed that TF3 significantly promoted the expression of VEGFA,SPOCD1,NGF,and NGFR in HUVECs.In MC3T3-E1 cells,the transcript levels of RUNX2 and COL2A1 were significantly elevated following TF3 treatment.Conclusion: TF3 promotes fracture healing by promoting bone regeneration associated with the RUNX2 pathway and angiogenesis associated with the VEGFA pathway.
文摘Geometry optimization and subsequent harmonic vibration calculations of prior synthesized （E）-3-（4-fluorophenyl）-N-[4-（phenyl-amino） quinazoline-7-yl] acrylamide were carried out by DFT/B3LYP method with both 6-31G and 6-311G basis sets.The Infrared （IR） spectrum of the title compound was recorded in the field of 400-4000 cm 1 and then assigned.The correlation analyses between the scaled theoretical vibration frequencies and the experimental ones indicate that there exist good linearity relationships since the correlation coefficients R 2 are larger than 0.999.The intramolecular interactions existed in the title molecule were confirmed by the Atoms in molecules （AIM） method,and their influences on the absorption frequency were also investigated.
