Cytotoxic effect of a non-peptidic small molecular inhibitor of the p53-HDM2 interaction on tumor cells

AIM: To investigate if non-peptidic small molecular inhibitors of the p53-HDM2 interaction could restore p53 function and kill tumor cells.METHODS: A series of non-peptidic small HDM2 inhibitors were designed by computer-aided model and synthesized by chemical method. Syl-155 was one of these inhibitors. Cytotoxic effect of syl-155 on three tumor cell lines with various states of p53, HT1080 (wild-type p53), KYSE510 (mutant p53), MG63 (p53 deficiency) was evaluated by MTT assay, Western blot and flow cytometry.RESULTS: Syl-155 stimulated the accumulation of p53 and p21 protein in HT1080 cells expressing wild-type p53, but not in KYSE510 and MG63 cells. Consequently, syl-155 induced cell cycle arrest and apoptosis in HT1080 cells.CONCLUSION: Non-peptidic small molecular inhibitors of the p53-HDM2 interaction show promise in treatment of tumors expressing wild-type p53.

In Silico Screening of Potential Inhibitors against dPLA2 from Named Chinese Herbs for Identification of Compounds with Antivenom Effects Due to Deinagkistrodon acutus Snake Bites

Phospholipase A2 (PLA2) is the key enzyme to the venom from Deinagkistrodon acutus which is one of the highly venomous snakes in China. In addition to being a catalyst for the hydrolysis of phospholipases A2 from snake venom, its well known that it possesses a broad spectrum of pharmacological activities, such as myotoxicity, neurotoxicity, cardiotoxicity, and hemolytic, anticoagulant and antiplatelet activities. However, snakebites are not efficiently treated by conventional serum therapy. Acute wounds can still cause poisoning and death. In order to find effective inhibitors of Deinagkistrodon venom acid phospholipase A2 (dPLA2), we obtained 385 compounds in 9 Chinese herbs from the TCMSP. These compounds were further performed to virtual screen using in silico tools like ADMET analysis, molecular docking and molecular dynamics (MD) simulation. After Pharmacokinetics analysis, we found 7 candidate compounds. Besides, analysis of small molecule interactions with dPLA2 confirmed that the amino acid residues HIS47 and GLY29 are key targets. Because they bind not only to the natural substrate phosphatidylcholine and compounds known for having inhibitory functions, but also for combining with potential antidote molecules in Chinese herbal medicine. This study is the first to report experience with virtual screening for possible inhibitor of dPLA2, such as the interaction spatial structure, binding energy and binding interaction analysis, these experiences not only provide reference for further experimental research, but also have a guideline for the study of drug molecular mechanism of action.

Molecular Docking and 3D-QSAR Research of Biphenyl Carboxylic Acid MMP-3 Inhibitors

The molecular docking by LigandFit docking of Discovery Studios 2.5 was employed to the three-dimensional quantitative structure-activity relationship（3D-QSAR） studies of biphenyl carboxylic acid MMP3 inhibitors.A significant correlation coefficient was obtained between dock scores and biological activities.Based on the optimal docking conformations,3D-HoVAIF was employed to the QSAR studies of 51 biphenyl carboxylic acid MMP-3 inhibitors.R2 and Q_CV2（leave-one-out,LOO） of the optimal 3D-HoVAIF-PLS model were 0.873 and 0.841 respectively.The conclusions obtained from the PLS analysis were in agreement with the docking results.

Pharmacokinetic evaluation,molecular docking and in vitro biological evaluation of 1,3,4-oxadiazole derivatives as potent antioxidants and STAT3 inhibitors

1, 3, 4-Oxadiazole derivatives(4 a–5 f) were previously synthesized to investigate their anticancer properties.However, studies relating to their antioxidant potential and signal transducer and activator of transcription(STAT) inhibition have not been performed. We investigated previously synthesized 1, 3, 4-oxadiazole derivatives(4 a–5 f) for various radical scavenging properties using several in vitro antioxidant assays and also for direct inhibition of STAT3 through molecular docking. The data obtained from various antioxidant assays such as 2, 2,-diphenyl-1-picrylhydrazyl radical(DPPH), nitric oxide, hydrogen peroxide, and superoxide anion radical revealed that among all the derivatives, compound 5 e displayed high antioxidant activities than the standard antioxidant L-ascorbic acid. Additionally, the total reduction assay and antioxidant capacity assay further confirmed the antioxidant potential of compound 5 e. Furthermore, the molecular docking studies performed for all derivatives along with the standard inhibitor STX-0119 showed that binding energy released in direct binding with the SH2 domain of STAT3 was the highest for compound 5 e(-9.91 kcal/mol).Through virtual screening, compound 5 e was found to exhibit optimum competency in inhibiting STAT3 activity. Compound 5 e decreased the activation of STAT3 as observed with Western blot. In brief, compound5 e was identified as a potent antioxidant agent and STAT3 inhibitor and effective agent for cancer treatment.

Microwave-assisted Solid-phase Synthesis, Biological Evaluation and Molecular Docking of Angiotensin I-converting Enzyme Inhibitors

Short peptides based on the tripeptides, Leu-Arg-Pro and Leu-Lys-Pro, were synthesized by microwave assisted solid-phase synthesis method, in order to make a search for potential inhibitors for angiotensin I-converting enzyme（ACE） with minimum side effects in the treatment of hypertension. One peptide with the sequence Leu-Arg-Pro-Phe-Phe shows the strongest inhibition towards ACE with an IC50 value of 0.26 μmol/L in vitro. The study of structure-activity relationship shows that the introduction of a bulky group into the N-terminal of this series of inhibitors may enlarge steric hindrance, resulting in the poor inhibitory activity towards ACE. The inhibitory activity decreased in turn when L-Pro, D-Pro or Ac6c was at the C-terminal respectively. The binding interaction between each of these inhibitors and testicular ACE（tACE） was performed by molecular docking. The results suggest that Leu-Arg-Pro-Phe-Phe mainly occupied the S1 subsite of tACE, and made contact with tACE via seven H-bonds. It appeared that the site on the peptide that bound with tACE was influenced by the configuration of the amino acid, L or D-form, at the C-terminal of the peptide.

Identification of α-glucosidase inhibitors from Clinacanthus nutans leaf extract using liquid chromatography-mass spectrometry-based metabolomics and protein-ligand interaction with molecular docking

The present study used in vitro and in silico techniques, as well as the metabolomics approach to characterise α-glucosidase inhibitors from different fractions of Clinacanthus nutans. C. nutans is a medicinal plant belonging to the Acanthaceae family, and is traditionally used to treat diabetes in Malaysia. nHexane, n-hexane: ethyl acetate(1:1, v/v), ethyl acetate, ethyl acetate: methanol(1:1, v/v), and methanol fractions were obtained via partitioning of the 80% methanolic crude extract. The in vitro α-glucosidase inhibitory activity was analyzed using all the fractions collected, followed by profiling of the metabolites using liquid chromatography combined with mass spectrometry. The partial least square(PLS) statistical model was developed using the SIMCA P^+14.0 software and the following four inhibitors were obtained:(1) 4,6,8-Megastigmatrien-3-one;(2) N-Isobutyl-2-nonen-6,8-diynamide;(3) 1′,2′-bis(acetyloxy)-3′,4′-didehydro-2′-hydro-β, ψ-carotene; and(4) 22-acetate-3-hydroxy-21-(6-methyl-2,4-octadienoate)-olean-12-en-28-oic acid. The in silico study performed via molecular docking with the crystal structure of yeast isomaltase(PDB code: 3 A4 A) involved a hydrogen bond and some hydrophobic interactions between the inhibitors and protein. The residues that interacted include ASN259, HID295, LYS156, ARG335,and GLY209 with a hydrogen bond, while TRP15, TYR158, VAL232, HIE280, ALA292, PRO312, LEU313,VAL313, PHE314, ARG315, TYR316, VAL319, and TRP343 with other forms of bonding.

Molecular Modeling Studies of Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors Combining Molecular Docking and 3D-QSAR Methods

The vascular endothelial growth factor （VEGF） and its receptor tyrosine kinases VEGFR-2 or kinase insertdomain receptor （KDR） have emerged as attractive targets for the design of novel anticancer agents. In the present work, molecular docking method combined with three dimensional quantitative structure-activity relationships （comparative molecular field analysis （CoMFA） and comparative molecular similarity indice analysis （CoMSIA）） to analyze the possible interactions between KDR and those derivatives which acted as selective inhibitors. The CoMFA and CoMSIA models gave a cross-validated coefficient Q2 of 0.713 and 0.549, non-cross-validated R2 values of 0.974 and 0.878, and predicted R2 values of 0.966 and 0.823, respectively. The 3D contour maps generated by the CoMFA and CoMSIA models were used to identify the key structural requirements responsible for the biological activity. The information obtained from 3D-QSAR and docking studies were very helpful to design novel selective inhibitors of KDR with desired activity and good chemical property.

Discovery and design of cyclic peptides as dengue virus inhibitors through structure-based molecular docking

Objective:To find potential peptide inhibitors against the NS2B/NS3 protease of DENV which in turn,can inhibit the viral replication inside host cell.Methods:Cyclic peptides were designed having combination of positively charged amino acids using ChemSketch software and were converted to 3D structures.DENV NS3 protein structure was retrieved from Protein Data Bank(PDB)using PDB Id:2FOM.DENV NS3 and cylic peptides were docked using MOE software after structural optimization.Results:Through molecular docking it was revealed that most of the peptides bound deeply in the binding pocket of DENV NS2B/NS3 protease an had interactions with catalytic triad.Peptide 2 successfully blocked the catalytic triad of NS2B/NS3 protease.Peptide 1,,4 and 6 also had potential interactions with active residues of the NS2B/NS3 protease while all other peptides were in close contact with the active sites of NS2B/NS3 protease thus,these peptides can serve as a potential drug candidate to stop viral replication.Conclusions:Thus.it can be concluded from the study that these peptides could serve as important inhibitors to inhibit the viral replication and need further in-vitro investigations to confirm their efficacy.

Comprehensive 3D-QSAR and Binding Mode of DAPY Inhibitors Using R-group Search and Molecular Docking

The diarylpyrimidine(DAPY) compounds are important in the nonnucleoside reverse enzyme inhibitors. The present study is aimed at studying the three-dimensional quantitative structure-activity relationship(3D-QSAR) of DAPY inhibitors and their binding mode. We build a 3D-QSAR model involving 24 training DAPY inhibitors based on Topomer CoMFA, and 8 molecules are employed to validate the external predictive power of the model obtained. The multiple correlation coefficients of fitting, cross-validation and external validation were 0.979, 0.597 and 0.756, respectively. Topomer Search was employed as a tool for virtual screening in drug-like compounds of ZINC database(2012). Finally, we successfully design 30 new molecules with higher activity than that of all training and test inhibitors. The results indicated that Topomer CoMFA model had both favorable estimation stability and good predictive capability. Topomer Search technology could be effectively used to screen and design new compound, and had good predictive capability to guide the design of new Anti-HIV drugs. The molecular docking method was also used to study the interactions of these drugs by docking the ligands into HIV-1 reverse transcriptase active site, which revealed the likely bioactive conformations. This study showed extensive interactions between the DAPY derivatives and MET230, TRP229, PHE227, TYR318, TYR183, PRO95, GLY99, ILE100,TYR188, VAL106, TYR181, GLY190, GLU138, VAL179, THR139, ASN103 and LYS101 residues in the active site of HIV-1 reverse transcriptase. These results provide useful insights for the design of potent new inhibitors of HIV-1 reverse transcriptase.

Molecular docking investigation for Indonesian H274Y mutant neuraminidase type 1 with neuraminidase inhibitors

The aim of this study is to get insight the interaction between Indonesian H274Y mutant neuraminidase with four inhibitors. Not only to seek preferable inhibitor to be used, but also to investigate the interaction occurred, especially hydrogen bonds formed. Hydrogen bonds analysis and its interaction energies calculation showed that zanamivir is the most preferable inhibitor with 13 hydrogen bonds formed and –439.96 kcal/mol. Laninamivir would be an alternative inhibitor since it has 10 hydrogen bonds and –307.19 kcal/mol. The investigation of ΔSAS showed almost all active site residues buried when interacted with inhibitors. Only a few residues have an increases ΔSAS. Lipinski rule analysis showed that zanamivir and laninamivir would be best taken by injection or inhalation.

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.

Molecular Docking Studies of Estrone-Coumarin Derivatives as Aromatase and 17β-HSD1 Inhibitors Related to Hormone Receptor Positive (HR+) Breast Cancer

Hormone Receptor positive (HR+) breast cancer is the most common malignancy in women. New strategies in the treatments have targeted the estrogen biosynthesis pathways including the inhibition of the aromatase and 17β-HSD1 enzymes. The present work, describes the study of a new family of 9 hybrid compounds derived from estrone attached to a coumarin fragment, linked through different lengths of hydrocarbon chains. The activity of these compounds was evaluated by molecular docking with two relevant enzymes in breast cancer (HR+). It has been proposed nine compounds as 17β-HSD1 inhibitors and six as aromatase inhibitors. We found important interactions with key amino acids at the orthosteric site of each enzyme and their score values compared to the crystallographic ligand. The in silico analysis showed good score values in the proposed compounds, where the steroidal portion presented important interactions with Met374 and Tyr155 in aromatase and in 17β-HSD1 respectively. Highlighting Compounds 2, 5 and 8 with an aromatic ring at the C4 position of the coumarin moiety, which favored arene-H type interactions essential for protein-ligand recognition. In addition, the results related to the 17β-HSD1 enzyme demonstrated how the length of the linker influences the interaction;the best score was found for derivative 8 with a chain of 8 methylenes.

Biological characteristics and clinical management of uveal and conjunctival melanoma

Uveal and conjunctival melanomas are relatively rare tumors;nonetheless,they pose a significant risk of mortality for a large number of affected individuals.The pathogenesis of melanoma at different sites is very similar,however,the prognosis for patients with ocular melanoma remains unfavourable,primarily due to its distinctive genetic profile and tumor microenvironment.Regardless of considerable advances in understanding the genetic characteristics and biological behaviour,the treatment of uveal and conjunctival melanoma remains a formidable challenge.To enhance the prospect of success,collaborative efforts involving medical professionals and researchers in thefields of ocular biology and oncology are essential.Current data show a lack of well-designed randomized clinical trials and limited benefits in current forms of treatment for these tumors.Despite advancements in the development of effective melanoma therapeutic strategies,all current treatments for uveal melanoma(UM)and conjunctival melanoma(CoM)remain unsatisfactory,resulting in a poor long-term prognosis.Ongoing trials offer hope for positive outcomes in advanced and metastatic tumors.A more comprehensive understanding of the genetic and molecular abnormalities involved in the development and progression of ocular melanomas opens the way for the development of personalized therapy,with various potential therapeutic targets currently under consideration.Increased comprehension of the molecular pathogenesis of UM and CoM and their specificities may aid in the development of new and more effective systemic therapeutic agents,with the hope of improving the prognosis for patients with metastatic disease.

STARD7蛋白新型小分子抑制剂Lasiodin激活NRF2/EGR1通路诱导三阴乳腺癌铁死亡

目的探讨StAR相关脂质转移结构域包含7(STARD7)在三阴乳腺癌(TNBC)中的表达情况及其与预后的相关性。高通量筛选STARD7的小分子抑制剂,研究其小分子抑制剂对TNBC的影响及潜在分子机制。方法生物信息学分析STARD7在各亚型乳腺癌中的表达情况以及与预后的相关性。Westernblot和免疫组化检测细胞系以及临床TNBC样本中STARD7的表达情况。以STARD7为靶点,通过分子对接、体外蛋白纯化和体外分子互作实验,筛选并鉴定STARD7的小分子抑制剂。CCK8测定对照组(DMSO组)及1、2、5、10、20μmol/L浓度Lasiodin处理24 h后的TNBC细胞的存活率,确定最佳药物作用浓度。台盼蓝和YO-PRO-1染色测定各组细胞死亡率,Westernblot测定各组凋亡、铁死亡相关蛋白表达;RT-qPCR及Western blot分别测定NRF2、HO-1、KEAP1、EGR1的mRNA和蛋白表达。构建TNBC移植瘤模型并随机分为对照组、紫杉醇组(10 mg/kg)和Lasiodin组(10 mg/kg),分别处理后测定肿瘤体积、裸鼠体重,HE染色评价生物安全性。结果生物信息学分析及体外实验表明STARD7在TNBC组织及细胞中高表达,且与患者预后负相关(P<0.05);高通量筛选并鉴定出Lasiodin是STARD7的小分子抑制剂;Lasiodin对STARD7的抑制可能通过调控下游NRF2/EGR1通路相关蛋白的表达促使TNBC细胞发生铁死亡,同时伴有凋亡和坏死。体内实验证明Lasiodin能够抑制肿瘤生长(P<0.05),且未观察到明显的不良反应。结论STARD7可能在TNBC的进展中发挥重要的调控作用,Lasiodin为其小分子抑制剂,提示STARD7和Lasiodin分别可能成为治疗TNBC的潜在靶点和新型药物。

水合物动力学抑制剂合成及其作用机理的分子动力学模拟

针对现有动力学抑制剂耐受过冷度较低、对水合物生成的诱导时间短的问题,采用N-乙烯基吡咯烷酮(NVP)、N-乙烯基己内酰胺(NVCL)、甲基丙烯酸二甲氨乙酯(DMAEMA)3种单体,制备了水合物动力学抑制剂P(NVP-g-NVCL-g-DMAEMA);以模拟天然气水合物抑制过程中的过冷度和诱导时间为指标,优化了合成条件;用红外光谱仪表征了产物结构,利用分子动力学模拟软件模拟抑制过程,揭示水合物动力学抑制剂的作用机理。结果表明,NVP、NVCL、DMAEMA单体质量比为8∶20∶1,引发剂(过硫酸铵、亚硫酸氢钠质量比为1∶1)为单体总质量的0.5%,反应温度65℃,反应时间6 h为最佳反应条件且产物为目标产物。当该条件下合成的抑制剂加量为1.0%时,常压条件下可将水合物形成的过冷度从2.6℃提高到9.6℃,诱导时间从20 min延长至945 min。该抑制剂的作用机理主要是通过分子链上五元环及七元环上的双键氧和酯基上的双键氧与水分子形成氢键吸附从而抑制水合物的生成,其次分子链上的氮原子也可以形成氢键而吸附;另外,抑制剂的空间位阻也会阻碍水合物分子的聚集进而抑制水合物的结晶。该抑制剂不仅带有可形成氢键的活性基团,增强抑制剂对水合物笼的吸附性,还存在能影响甲烷分子运动及分布状态的烷基链,进一步提高过冷度并延长诱导时间。

单相缓速酸酸蚀裂缝导流规律

低渗碳酸盐岩酸压成功的关键在于酸压后形成可在地层闭合压力下保持高导流能力的酸蚀裂缝。单相缓速酸是一种具有纳米结构、低伤害、低摩阻及高缓速性能的新型酸液体系,应用潜力大,但其酸蚀裂缝导流规律尚不明确。以光滑岩板和粗糙岩板为实验对象,以盐酸、胶凝酸和乳化酸为对比,利用酸液刻蚀和酸蚀裂缝导流实验、表面形貌扫描和连续强度测试仪,研究了酸液类型、交替注入级数、注入速度、黏度比、反应时间、岩板类型对导流能力的影响。结果表明:单相缓速酸相对于盐酸、胶凝酸和乳化酸,可形成强沟道型刻蚀形貌,差异化溶蚀程度高,岩板强度损伤减缓,在高闭合压力下可保持较高的导流能力。提高酸液交替注入级数(≥3级)、注入速度、黏度比(黏度差≥50 mPa·s)及岩板初始表面粗糙度,有助于形成优势酸液流通通道。单相缓速酸实现高导流酸蚀裂缝机理为:(1)黏性指进形成差异化刻蚀沟道;(2)主蚓孔滤失形态及“虹吸”效应减缓裂缝表面强度损伤。

小分子胺对蒙脱石水化抑制作用的分子动力学模拟

蒙脱石水化是导致钻井过程中井壁失稳的重要原因,小分子胺常被用做钻井液抑制剂来抑制蒙脱石的水化,但小分子胺的抑制剂作用机理基本是通过对抑制性能的评价来间接验证和分析的。为了深入揭示小分子胺的抑制剂作用机理,本文利用分子动力学的方法建立小分子胺-蒙脱石的分子动力学模型,通过模拟动态抑制过程,计算水分子的均方位移、抑制剂的径向分布函数、体系的能量和蒙脱石力学参数来研究小分子胺的抑制剂作用机理。结果表明:可视化的动态抑制过程显示小分子胺占据水分子原本吸附位点,分子中部的疏水基团阻止水分子在一定范围内接近蒙脱石表面;均方位移表明小分子胺的加入抑制的水分子的扩散,并且在水化后期小分子胺抑制效果更好;径向分布函数图显示,羟甲基比胺基更易与蒙脱石表面裸露的氧原子吸附,而小分子胺中的胺基降低了蒙脱石表面的负电荷密度;体系能量变化显示,在水化后期小分子胺与蒙脱石表面的相互作用更强;力学参数变化显示,在小分子胺加入后,蒙脱石的弹性模量、剪切模量、杨氏模量变大,提高了蒙脱石晶体的结构稳定性。

基于药物拼接的verubulin衍生物的设计合成及活性评价

目的通过在verubulin(1)结构中的喹唑啉环2位引入MP-HJ-1c(3)结构中的吡咯并[2,3-d]噻唑-5-甲酰胺基团,发现新结构类型的微管聚集抑制剂。方法将化合物1的衍生物2和3与微管蛋白的复合晶体结构6BR1、5YZ3进行叠合,设计了分别用亚甲基或1,2-亚乙基将1喹唑啉环2位与3中吡咯并[2,3-d]噻唑-5-甲酰胺基进行连接得到的目标化合物4a和4b,并进行了分子对接。4a和4b经酰胺缩合、分子内成环、亲核取代和酰胺缩合4步反应合成,总收率分别为7.9%、11.3%,结构经^(1)H-NMR、^(13)C-NMR和HR-ESI-MS确证。评价了4a和4b对人肺癌细胞A549增殖的抑制活性和微管聚集的抑制活性。结果分子对接结果显示,4a与5YZ3的结合能为-27.93 kcal·mol^(-1),来源于1、3的结构部分各自基本维持了与微管蛋白的相互作用方式。4a和4b的A549增殖抑制活性分别为(0.15±0.03)μmol·L^(−1)和(9.91±1.04)μmol·L^(−1)(GI50值);仅4a表现出微弱的微管聚集抑制活性[(67.1±11.1)μmol·L^(−1)(IC_(50)值)]。结论设计的化合物4a表现出一定的体外肿瘤细胞增殖抑制活性和微管聚集抑制活性,可作为先导化合物,进一步对其结构中的N-甲基-4-甲氧基苯环部分进行构效关系研究。4b经体外测试无明显微管聚集抑制活性,与分子对接中由于连接链过长导致吡咯并[2,3-d]噻唑-5-甲酰胺基无法与微管蛋白形成有效相互作用的结果一致。

基于分子对接及动力学模拟的红曲橘霉素合成小分子抑制剂的高通量筛选

通过计算机模拟技术,对红曲橘霉素合成关键酶CitE的抑制剂进行高通量筛选。首先,采用Alphafold 2对CitE蛋白进行同源建模,并与相似序列比对以预测配体结合区域;随后,在Arthor数据库中检索天然配体和黄酮骨架类似物,构建了一个包含20000个化合物的配体库;之后,通过Maestro对CitE蛋白和小分子化合物库进行分子对接,筛选出潜在的CitE配体;并采用Gromacs动力学模拟评估结合稳定性,通过MM/PBSA计算结合自由能,之后对蛋白-配体的结合模式进行分析,进一步确定了槲皮素、木犀草素、芹菜素、染料木素、5,4’-二羟基黄酮、漆黄素6个小分子配体具有较强的CitE结合性能。固态及液态发酵结果表明,上述化合物具有显著的橘霉素抑制活性。其中,固态发酵(20mg/28g干物料)添加上述化合物分别使橘霉素产量降低42.52%、48.81%、32.54%、32.57%、21.02%和13.67%,液态发酵添加(0.1 g/L)上述化合物分别使橘霉素产量降低33.77%、15.58%、33.33%、62.34%、58.87%、50.22%。本研究对建立高效、安全的红曲发酵体系具有借鉴意义。

富含双键咪唑啉在饱和CO_(2)盐水中缓蚀行为研究

目的合成含有两个双键的亚油酸咪唑啉,与传统的含有单个双键油酸咪唑啉对比,研究其结构对其缓蚀性能的影响。方法在60℃下将Q235钢浸泡于饱和CO_(2)的3%(w)NaCl溶液中,通过失重、电化学测试和缓蚀效率测试,并通过表面分析方法观察腐蚀后钢片形貌变化,最后通过理论计算对合成缓蚀剂进行性能研究。结果电化学与失重结果显示在加入质量浓度为200 mg/L的亚油酸咪唑啉后,缓蚀效率能达到90%,缓蚀性能优于常见的油酸咪唑啉。在结构上,由于亚油酸咪唑啉分子比油酸咪唑啉多了一个双键,增加了咪唑啉缓蚀剂的吸附位点,使其能更好地吸附于金属的表面。结论亚油酸咪唑啉对碳钢有很好的缓蚀性能;在同等实验条件下,缓蚀性能优于油酸咪唑啉;其吸附满足Langmuir吸附等温线;吸附过程中主要通过N—Fe键吸附在Fe表面。