Synthesis, Characterizations, Biological, and Molecular Docking Studies of Some Amino Acid Schiff Bases with Their Cobalt(II) Complexes

The synthesis and structural characterization of cobalt(II) complexes of amino acid Schiff bases was prepared from Salicylaldehyde and three amino acid (Valine, Leucine, and Isoleucine)?in basic medium. The metal complexes was synthesized by treating an ethanolic solution of the ligand with appropriate amount of metal salts [1:2] [M:L] ratio. The synthesized Schiff bases and their metal complexes have been investigated on the bases of elemental chemical analysis, FTIR, electronic spectral,?1HNMR,?13CNMR, MS, molar conductance and magnetic susceptibility measurements. The electronic spectra of the metal complexes and their magnetic susceptibility measurements suggest octahedral structures are the probable coordination geometries for the isolated complexes. The Schiff bases and their metal complexes were preliminary scanned against various strains of microbes to study their biological effect.

Binding of Quinoline-Based Inhibitors to <i>Plasmodium falciparum</i>Lactate Dehydrogenase: A Molecular Docking Study

Development of new antimalarial drugs continues to be of great importance due to the resistance of the malaria parasite to currently used drugs. Glycolytic enzymes have emerged as potential targets for the development of new drugs due to the reliance of the parasite on glycolysis for energy. In this study, molecular docking was used to study the binding of some quinoline-based drugs to the glycolytic enzyme lactate dehydrogenase. The docking studies identified two potential binding sites for each ligand, one of them being the cofactor-binding site. For all ligands studied, there was the comparable binding to the cofactor-binding site as well as the secondary binding site when the cofactor was absent. All ligands showed significantly lower binding affinity than NADH for the cofactor binding site. The alternative site was the site of preference when docking was done in the presence of the cofactor. While binding to the cofactor site may support other studies suggesting potential for competitive inhibition, the fact that the binding affinities of all the ligands are significantly lower than that for NADH in this site suggests that these ligands will be ineffective competitive inhibitors. The identification of an alternative binding site with comparable affinity that is not affected by the presence of the cofactor may suggest the possibility of non-competitive inhibition that requires further exploration.

Novel 1,3,4-(thiadiazol-2-ylamino) methyl-5-(pyridin-4-yl)-1,3,4-oxadiazol-2-thiones: synthesis, docking and antimycobacterial testing

In the present study, a novel series of Mannich bases of 3-substituted 5-(pyridin-4-yl)-1,3, 4-oxadiazol-2-thione derivatives were synthesized. Docking study was performed to rationalize the possible interactions between the synthesized com-pounds and active site of 14DM. The test compounds were screened for antimycobacterial activity using Middlebrook 7H9 medium against M. tuberculosis H37Rv (ATCC 27294) as well as Isoniazid (INH) resistant clinical strain. Among the series 5c and 5a are found to be most potent (susceptible) while the compound 5f did not show activity against M. tuberculosis H37Rv (resistant). The SAR study reveals the importance of substitutions at para position for good activity.

Molecular Docking Studies on Anticonvulsant Enaminones Inhibiting Voltage-Gated Sodium Channels

Epilepsy is described as the most common chronic brain disorder. A typical symptom of epilepsy results in uncontrolled convulsions caused by temporary excessive neuronal discharges. Although several new anticon-vulsants have been introduced, some types of seizures have still not been adequately controlled with these new and current therapies. There is an urgent need to develop new anticonvulsant drugs to control the many different types of seizures. Many studies have shown that the epilepsies involve more than one mechanism and therefore may be responsible for the various types of observed seizures. Recently reported studies have shown that a group of newly synthesized 6 Hz active anticonvulsant fluorinated N-benzamide enaminones exhibited selective inhibitions of voltage-gated sodium (Nav) channels. Nav channels are responsible for the initial inward currents during the depolarization phases of the action potential in excitable cells. The activation and opening of Nav channels result in the initial phases of action potentials. We hypothesize that there is an essential pharmacophore model for the interactions between these enaminones and the active sites of Nav channels. The research reported here is focused on molecular docking studies of the interactions that occur between the fluorinated N-benzamide enaminones and the Nav channels. These studies may open an avenue for designing anticonvulsant drugs by inhibiting Nav channels.

双Schiff-Base取代的3,5-二(芳亚甲基)-4-哌啶酮衍生物的合成及活性研究

通过Claisen-Schmidt缩合、Sn Cl2/HCl还原和Schiff-Base缩合反应得到9个双Schiff-Base取代的3,5-二(芳亚甲基)-4-哌啶酮衍生物(3a-i),并通过核磁共振(NMR)、傅立叶变换红外光谱(FTIR)、元素分析进行结构表征,采用MTT法,评价其对SGC-7901(胃癌细胞)、A549(肺癌细胞)、HCT116(结肠癌)、He La(宫颈癌细胞)、He PG2(肝癌细胞)、K562(人慢性骨髓性白血病细胞)、THP-1(人急性单核粒细胞白血病细胞)、U937(组织细胞淋巴瘤细胞)、MCF-7(乳腺癌细胞)等细胞系的抗肿瘤活性以及对LO2(人正常肝细胞)的细胞毒性。结果显示,部分化合物对某些细胞的IC50值小于1.0μmol/L。细胞毒性实验显示,化合物3a,d-f对正常细胞LO2的细胞毒性比阿霉素(DOX)小。构效关系显示F取代的化合物3a-c活性优于Br和Cl取代的化合物3d-i。通过PCR、Western Blot以及分子对接模型初步说明3b和3i对Bcl-2蛋白有显著的抑制作用。

Synthesis, Characterization, Antimicrobial and DNA Binding Studies of a Tetradentate N2O2 Amino Acid Schiff Base and Its Coordination Compounds

Aminoethanoic acid undergoes condensation with 1,4-benzenedicarboxaldehyde to form an O, N, N, O donor Schiff base, N,N'-di(carboxymethylene) terephthalaldehyde, Ligand L. Coordination compounds of this Schiff base using Ni (II), Cu (II), VO (IV) and Co (II) were then obtained in-situ. The Schiff base and the complexes were evaluated for their antimicrobial and DNA binding abilities. Molecular docking studies of the ligand and synthesized compounds were also carried out. Evidence for the formation of the Schiff base coordination compounds and the coordinating atoms was obtained from 1H NMR, infrared and ultraviolet spectral data, EDX, EDTA complexometric titration and magnetic susceptibility measurement. The results obtained are consistent with octahedral geometry for Ni (II) complex, the metal ion coordinating to one molecule of Ligand L and with additional coordination with two oxygen atoms of two molecules of the solvent. A square-planar geometry was suggested for both Co (II), and Cu (II) complexes and a five-coordinate, square pyramidal geometry for the VO (IV) complex. The results further indicated that the carboxylic acid of Ligand L was not deprotonated both in the free base and also the complexes. In addition, the results showed that Compound 2 elicited the best antimicrobial activity potential. Generally, the compounds exhibited considerable good affinity to CT-DNA.

芹菜籽中芹菜素曼尼希碱衍生物抗高尿酸血症活性研究

本文旨在探究芹菜籽中降尿酸活性成分芹菜素曼尼希碱衍生物对高尿酸血症小鼠模型的降尿酸作用及其机制。通过分子对接分析,氧嗪酸钾-酵母膏诱导高尿酸血症小鼠体内试验,探索芹菜素Mannich碱衍生物8-(4-乙基哌嗪-1-甲基)-5,7-二羟基-2-(4-苯酚)-4H-1-苯并吡喃-4-酮(APN083)的抗高尿酸血症作用。结果表明,灌胃给予高尿酸血症小鼠高、中浓度(15 mg/kg、7.5 mg/kg)APN083能明显降低血清尿酸水平(P <0.05),能显著降低血清CRE水平,具有显著的降尿酸作用,能在一定程度上抑制黄嘌呤氧化酶(XO)活性,并且促进尿酸的排泄;通过分子对接分析,该化合物通过结合到XO的活性空腔,并与周围氨基酸相互作用,从而阻碍底物分子进入活性中心,降低酶的催化活性。芹菜素曼尼希碱衍生物APN083具有较好的降尿酸作用,能从一定程度上抑制XO活性。

高职教育教学标准与职业岗位标准对接研究——以电子商务专业为例

以建设技能型社会为背景,以漯河职业技术学院电子商务专业为研究对象,从分析当前电子商务专业教学标准与职业岗位标准对接现状入手,梳理电子商务专业教学标准与职业岗位标准对接实践中的主要问题,反思现状,探究根源,找出阻碍有效对接问题的原因所在,构建一套可推广、可复制的电子商务专业教学标准与职业岗位标准对接实施路径模板,促进电子商务专业人才培养工作高质量提升,突出河南省高水平电子商务专业群的引领和示范作用,培养更多高素质技术技能人才和能工巧匠,有效助推技能型社会建设。

枯草芽孢杆菌漆酶与阴离子型聚丙烯酰胺微观作用机理

阴离子型聚丙烯酰胺(HPAM)常用于煤泥水的澄清处理,产生大量的含聚污水将对选煤厂周边环境造成不利影响.为探究漆酶降解HPAM的微观作用机理,采用对接模拟了HPAM及其脱氨产物聚丙烯酸(PAA)结构模型与枯草芽孢杆菌漆酶(Lac)的结合,根据-CDOCKER_Energyscore打分最高原则筛选出Lac的最适底物,然后对该最适复合物分别进行基于亲和力虚拟突变和不同温度下的分子动力学(MD)模拟.结合模式分析表明,Lac对HPAM-3享有最高亲和力,且其结合最好,因此HPAM-3是该酶的最适底物;HPAM比PAA易被Lac降解;Lac可容纳一定碳链长度的HPAM和PAA.相互作用分析表明,Lac-HPAM-3亲和力最大主要原因是盐桥;TYR133通过形成氢键以稳定Lac-HPAM-2、Lac-HPAM-3和Lac-HPAM-4,而ARG487通过形成疏水以稳定所有的酶-底物复合物.基于亲和力虚拟突变分析表明,TYR118、TYR133、ARG487和LYS135是Lac降解HPAM-3的关键残基;LYS135和ARG487分别通过形成盐桥和疏水来最大限度地影响酶同底物的亲和力.MD分析表明,Lac-HPAM-3在298 K时总相互作用能、酶骨架RMSD及所有残基RMSF皆最低,因此该复合物在298 K时结合稳定性最佳;308 K时由于酶骨架RMSD最大,导致底物偏离最初对接位置,因此Lac-HPAM-3在308 K时结合稳定性最差.这些数据为揭示HPAM酶降解过程奠定基础,为将来突变试验来改造酶提供位点支持.

传统和机器学习策略在基于结构虚拟筛选中的应用

计算机辅助药物发现和人工智能驱动药物设计在制药行业中是减少时间和经济成本的重要策略.其中具有代表性的方法包括虚拟筛选、蛋白质-配体相互作用评估、药物药代动力学性质预测以及药物设计.通常来说,虚拟筛选是药物发现的第一步,其主要目标是识别和发现潜在的先导化合物的候选物.在过去的几十年里,已经开发了多种传统的和基于机器学习的方法来提高虚拟筛选的准确性和速度.本综述总结了传统和机器学习方法在基于结构的虚拟筛选中的应用,讨赖性较弱,且分布非常冷并在j=1处达到峰值,但(0,1,0)振动态的转论了它们的性能、优势和局限性等方面.

1,8-二川芎嗪基大黄酸与牛血清白蛋白相互作用研究

本文采用紫外光谱法、荧光光谱法、圆二色谱法、电化学分析法和分子对接技术,对1,8-二川芎嗪基大黄酸(DBR)与牛血清白蛋白(BSA)的相互作用机制进行了研究。结果表明DBR和BSA间存在强相互作用,在温度290、300、310 K时,两者间的结合常数Ka的数量级达10^(5),结合位点数为1.1,表明两者之间有着较强的相互作用并形成1∶1复合物;Kq两者的猝灭常数值分别为5.5924×10^(12)、4.9853×10^(12)、4.1665×10^(12)L·mol^(-1)·s^(-1),推测猝灭方式为静态猝灭。根据F9rster的非辐射能量转移机制求算出给体与受体间的结合距离r=4.8 nm、能量转移效率E=0.5793,推测两者之间存在非辐射能量转移;通过计算该体系的热力学参数得到ΔH<0,ΔS<0,ΔG<0,表明二者作用力类型为氢键和范德华力。另外,随着DBR的加入BSA的构象发生了改变,BSA的α-螺旋结构从60.55%减少到58.5%;电化学分析法表明两者形成了非电活性的超分子化合物;分子对接模拟结果推测出DBR分子进入了BSA分子的疏水腔内,其结合位置位于domainⅠA亚域。

岸基LNG加注码头与LNG码头本质差异对比及设计要点

为系统研究分析岸基LNG加注码头和LNG码头的关键差异,为设计提供针对性的理论依据,采用规范分析、实践类比、逻辑推理等方法,分析两种码头在代表船型、港址选择、作业工艺、作业量等方面的本质差异,提出安全设计、消防设计方面的总体设计要点。结果表明,岸基LNG加注码头有别于普通货类码头和危险货物码头,是一种特殊性质的港口支持性码头;码头火灾危险性及消防设计宜制定针对性的防火规范,火灾危险性为甲A类,消防设计按照扑灭码头自身初期火灾要求配置;采用水上补给或水陆联合补给时,不改变其加注码头主体性质,合理参照LNG码头做法,做好安全应急预案及现场安全管理。

基于网络药理学和分子对接的补肾固齿丸治疗肾虚血热型牙周病物质基础与作用机制研究

[目的]通过网络药理学及分子对接分析,揭示了补肾固齿丸治疗肾虚血热型牙周病的有效物质基础及作用机制。[方法]通过中药系统药理学数据库与分析平台(TCMSP)等数据库及平台检索补肾固齿丸复方中各味药材的所有有效成分及相应靶标,在人类基因数据库(Gene Cards)及在线《人类孟德尔遗传》(OMIM)平台检索疾病相关靶基因,构建补肾固齿丸“活性成分-成分对应靶标-牙周病靶标”网络,进一步筛选进行网络拓扑学分析,并对有效核心成分及关键靶标进行分子对接,分析小分子配体与受体的结合能力。[结果]筛选出12个活性成分,25个靶标,关键靶标3个,分别为雌激素受体(ESR1)、表皮生长因子受体(EGFR)、磷酸肌醇3-激酶α(PIK3CA)。这些成分及靶标基因通过对核受体活性、蛋白激酶活性、酶激活剂活性、生长因子结合、血红素结合、内肽酶活性、蛋白质同二聚活性等的调节,参与细胞肿瘤抗原(P53)及核因子κB(NF-κB)信号通路的调控过程对牙周病的治疗起到重要作用。分子对接分析发现,3个关键靶标与12个活性成分(Quercetin、Aureusidin、Physcion等)均具有一定的亲和力。[结论]补肾固齿丸通过复杂的网络调控对肾虚血热型牙周病的起到有效治疗作用,该研究为更进一步探索其治疗相关证候的作用机制及临床应用提供了研究思路和理论基础。

一种新的自组装模块化群体机器人——对接机构设计与自组装控制

基于新型自组装模块化群体机器人Sambot,研究并实现了多个机器人之间的自主对接与自组装控制.首先,提出了一种由对接卡扣与对接卡槽组成的新型对接机构,它可以使多个Sambot在一定对接偏差范围内,从前、后、左、右4个方向同时进行对接;其次,采用基于行为的控制方法,仅依赖机器人自身红外传感器的局部感知和通信能力,实现了对接机器人寻找目标、导航和自主对接等自组装行为;最后,成功完成了两个Sambot的自主对接与自组装控制实验.实验结果表明,本文提出的自组装控制方法可以直接扩展到多个Sambot的情形,来构建任意构型的集合体机器人.

MoS_2在空间对接摩擦材料烧结过程中的行为变化

采用粉末冶金技术制备了空间对接用铜基摩擦材料,利用X射线衍射及定量化学分析技术对MoS2在材料烧结过程中的变化行为及与其他组元之间的作用进行研究。结果表明,MoS2在加压烧结过程中存在三个方面的反应:在高温下分解成Mo和S,并造成了S元素的损失;与Cu作用形成了复杂的铜钼硫化合物;与Cu反应生成了Cu的硫化物,该类化合物具有与MoS2相类似的层状结构,有一定的润滑作用。MoS2高温分解后或MoS2与Cu反应产生的Mo元素与石墨反应形成了Mo的碳化物。另外,双飞粉的加入不仅与材料中的Mo元素作用形成CaMoO4,并且改变了铜钼硫化合物、Cu的硫化物以及Mo的碳化物中各元素的摩尔比。

基于分子对接和QSAR方法预测B-Raf Ⅱ型抑制剂活性

B-Raf激酶在促分裂素原活化蛋白激酶(MAPK)信号转导通路中起着重要作用,已被确定为癌症治疗非常有吸引力的靶标.新型高效B-Raf抑制剂的开发成为癌症治疗的一个热门研究领域.本文以结构多样的B-Raf II型抑制剂为研究对象,联合应用分子对接和定量构效关系(QSAR)模型研究其定量构效关系去探讨抑制活性的起源.两个主题作为研究重点:生物活性构象和描述符.首先对分子对接方法(Glide、Gold、Ligand Fit、Cdocker和Libdock)进行准确性评价,后将研究的对象分子对接到B-Raf活性位点并获得生物活性构象.基于准确的对接结果,计算得到16个打分评价函数和21个能量描述符,以此构建定量构效关系模型.QSAR结果表明模型具有高度精确的拟合和强的预测能力(模型M1:r2=0.852,=0.790,=0.864;模型M2:r2=0.738,=0.812,=0.8605).同时探讨了对抑制活性有重要影响的描述符,结果表明打分评价函数(G_Score,-ECD,Dock_Score,PMF)与能量描述符(S(hb_ext),DE(int),Emodel)对抑制活性影响非常大.通过虚拟筛选和QSAR模型理论预测,一些新的具有潜在抑制活性的化合物作为B-Raf II型抑制剂被获得.上述信息对于进一步设计新颖高效的B-Raf II型抑制剂提供了有用的指导.

植物挥发性有机物数据库的建立及应用

通过收集已有植物挥发性有机物信息,利用MDL ISIS Base化学信息管理系统,构建了植物挥发性有机物数据库;同时,运用Discovery Studio模拟结合板块,对数据库进行了虚拟筛选。该数据库包含2 410个挥发性有机物的分子式、结构式、分子质量、CAS号等基本参数;以斜纹夜蛾普通气味结合蛋白Ⅱ(SlitGOBPⅡ)为靶标,应用此数据库对其进行虚拟筛选并得到6个备选活性化合物,其中泼尼松(prednisone)和SlitGOBPⅡ能够结合成稳定的复合物。植物挥发性有机物数据库的构建,以及Discovery Studio的分子模拟对接技术的应用,可为今后新型农药的研制提供理论依据。

航天器自主交会对接的视觉相对导航方法

针对航天器自主交会对接在最终逼近阶段的相对导航问题,研究了基于特征光标的航天器视觉相对导航方法。首先建立了小角度假设条件下的相对导航模型。给出了航天器相对位置和采用欧拉角描述的相对姿态的近似解析算法。其次利用相对姿态的解析解作为观测信息,采用降阶的无迹卡尔曼滤波方法对目标航天器的姿态角和惯性角速度进行了估计,间接得到了相对姿态和相对姿态角速度的估计值。数值仿真表明提出的解析算法能够有效获得相对位置和相对姿态测量信息,通过降阶滤波可明显提高相对姿态确定精度。

大型沉管隧道干坞的设计与研究

文章主要从干坞的选址、方案比选、防汛体系、边坡、基底处理以及边坡稳定计算和基底变形计算等方面总结了干坞设计的一些经验。

压力对空间对接摩擦材料摩擦磨损性能的影响

通过粉末冶金方法制备了铜基摩擦材料,在经技术改进后的MM-1000摩擦试验机上对其在不同压力下的摩擦磨损性能进行了研究,结果表明:随着压力的增大,材料的摩擦系数呈降低趋势,在真空中的摩擦系数小于大气中的摩擦系数;真空中材料的摩擦系数稳定度高于大气环境中的,材料的磨损随压力的变化在两种环境下呈现出相反的变化形式。摩擦表面形成的摩擦膜对材料的摩擦磨损性能具有重要的影响;随着压力的增大,材料在真空中的磨损机理由以磨粒磨损为主逐渐转变为以黏着磨损为主。