Characterization of the Anti-Biofilm and Anti-Quorum Sensing Activities of the β-Adrenoreceptor Antagonist Atenolol against Gram-Negative Bacterial Pathogens

The development of bacterial resistance to antibiotics is an increasing public health issue that worsens with the formation of biofilms. Quorum sensing (QS) orchestrates the bacterial virulence and controls the formation of biofilm. Targeting bacterial virulence is promising approach to overcome the resistance increment to antibiotics. In a previous detailed in silico study, the anti-QS activities of twenty-two β-adrenoreceptor blockers were screened supposing atenolol as a promising candidate. The current study aims to evaluate the anti-QS, anti-biofilm and anti-virulence activities of the β-adrenoreceptor blocker atenolol against Gram-negative bacteria Serratia marcescens, Pseudomonas aeruginosa, and Proteus mirabilis. An in silico study was conducted to evaluate the binding affinity of atenolol to S. marcescens SmaR QS receptor, P. aeruginosa QscR QS receptor, and P. mirabilis MrpH adhesin. The atenolol anti-virulence activity was evaluated against the tested strains in vitro and in vivo. The present finding shows considerable ability of atenolol to compete with QS proteins and significantly downregulated the expression of QS- and virulence-encoding genes. Atenolol showed significant reduction in the tested bacterial biofilm formation, virulence enzyme production, and motility. Furthermore, atenolol significantly diminished the bacterial capacity for killing and protected mice. In conclusion, atenolol has potential anti-QS and anti-virulence activities against S. marcescens, P. aeruginosa, and P. mirabilis and can be used as an adjuvant in treatment of aggressive bacterial infections.     

三类天然橡胶环氧官能化产物热行为的研究

本文用 Ｄ Ｓ Ｃ 及 Ｔ Ｇ 方法研究了３ 类天然橡胶环氧官能产物的热行为,结果表明,含有环氧基、羟基和呋喃基的 Ｅ Ｎ Ｒ－ Ⅱ以及含有羟基和呋喃基的 Ｅ Ｎ Ｒ－ Ⅲ在１４４ ～２２１ ℃的温度范围有明显的放热现象,其热焓分别为６７ ．３ 和１３８ ．４ Ｊ／ｇ ,在相同的条件下天然橡胶（ Ｎ Ｒ） 和含有环氧基的 Ｅ Ｎ Ｒ－ Ⅰ均无放热现象;在氮气氛中,低于２６０ ℃的温度下, Ｎ Ｒ、 Ｅ Ｎ Ｒ－ Ⅰ及 Ｅ Ｎ Ｒ－ Ⅱ均无明显失重, Ｎ Ｒ、 Ｅ Ｎ Ｒ－ Ⅰ、 Ｅ Ｎ Ｒ－ Ⅱ及 Ｅ Ｎ Ｒ－ Ⅲ的外延起始温度分别为３８０ ℃、３７０ ℃、３９８ ℃和３９０ ℃。     

几种天然产物在海洋防污涂料中的应用研究

将天然产物齐墩果酸、蛇床子素和鱼藤酮作为防污剂,分别制备海洋防污涂料,在厦门海域检验其海区防污效能,并与已报道在厦门海域具防污效能的天然产物喜树碱进行比较,发现蛇床子素和鱼藤酮在海区挂板2个月内显示出一定的防污效能,齐墩果酸没有呈现出防污效能,而喜树碱的海区防污效能明显优于上述3种天然产物。另外,将喜树碱与鱼藤酮进行1∶1复配,并将这2种天然产物与氧化亚铜、N-(2,4,6-三氯苯基)马来酰亚胺(TCPM)和吡啶硫铜锌(ZPT)这3种防污(助)剂分别进行1∶1复配,共获得7种复配防污剂,制备相应的海洋防污涂料以检测其防污效能,发现喜树碱-TCPM、喜树碱-ZPT以及喜树碱-鱼藤酮这3种复配防污剂具良好的防污效能。进一步在上述涂料中选取了防污效能最优的含喜树碱涂料,在福建东山海域和海南陵水海域分别进行了海区挂板试验,结果表明含喜树碱涂料在这2个海域均显示出稳定、优异的防污效能,且期效可达13个月以上。文中研究为推进天然防污产物在海洋防污涂料中的应用进程提供了重要资料。     

Natural Products of Marine Origin for the Treatment of Colorectal and Pancreatic Cancers: Mechanisms and Potential

Gastrointestinal cancer refers to malignancy of the accessory organs of digestion, and it includes colorectal cancer (CRC) and pancreatic cancer (PC). Worldwide, CRC is the second most common cancer among women and the third most common among men. PC has a poor prognosis and high mortality, with 5-year relative survival of approximately 11.5%. Conventional chemotherapy treatments for these cancers are limited due to severe side effects and the development of drug resistance. Therefore, there is an urgent need to develop new and safe drugs for effective treatment of PC and CRC. Historically, natural sources—plants in particular—have played a dominant role in traditional medicine used to treat a wide spectrum of diseases. In recent decades, marine natural products (MNPs) have shown great potential as drugs, but drug leads for treating various types of cancer, including CRC and PC, are scarce. To date, marine-based drugs have been used against leukemia, metastatic breast cancer, soft tissue sarcoma, and ovarian cancer. In this review, we summarized existing studies describing MNPs that were found to have an effect on CRC and PC, and we discussed the potential mechanisms of action of MNPs as well as future prospects for their use in treating these cancers.     

天然产物是农药新型活性结构的重要先导库

综述了以天然产物为先导化合物研发农药的概况。     

Bioengineering of Anti-Inflammatory Natural Products

Inflammatory processes occur as a generic response of the immune system and can be triggered by various factors, such as infection with pathogenic microorganisms or damaged tissue. Due to the complexity of the inflammation process and its role in common diseases like asthma, cancer, skin disorders or Alzheimer's disease, anti-inflammatory drugs are of high pharmaceutical interest. Nature is a rich source for compounds with anti-inflammatory properties. Several studies have focused on the structural optimization of natural products to improve their pharmacological properties. As derivatization through total synthesis is often laborious with low yields and limited stereoselectivity, the use of biosynthetic, enzyme-driven reactions is an attractive alternative for synthesizing and modifying complex bioactive molecules. In this minireview, we present an outline of the biotechnological methods used to derivatize anti-inflammatory natural products, including precursor-directed biosynthesis, mutasynthesis, combinatorial biosynthesis, as well as whole-cell and in vitro biotransformation.     

酶辅助提取技术在天然产物提取中的应用研究进展

酶辅助提取技术具有高效、特异性强、操作流程简便和条件温和等众多优势。介绍了生物酶的种类和特点,综述了酶辅助提取的作用机理、操作流程和影响因素,并归纳其在天然产物提取中的具体应用,旨在为工业化开发提供依据。     

Bacterial Tropone Natural Products and Derivatives: Overview of their Biosynthesis,Bioactivities, Ecological Role and Biotechnological Potential

Tropone natural products are non-benzene aromatic compounds of significant ecological and pharmaceutical interest. Herein, we highlight current knowledge on bacterial tropones and their derivatives such as tropolones, tropodithietic acid, and roseobacticides. Their unusual biosynthesis depends on a universal CoA-bound precursor featuring a seven-membered carbon ring as backbone, which is generated by a side reaction of the phenylacetic acid catabolic pathway. Enzymes encoded by separate gene clusters then further modify this key intermediate by oxidation, CoA-release, or incorporation of sulfur among other reactions. Tropones play important roles in the terrestrial and marine environment where they act as antibiotics, algaecides, or quorum sensing signals, while their bacterial producers are often involved in symbiotic interactions with plants and marine invertebrates (e. g., algae, corals, sponges, or mollusks). Because of their potent bioactivities and of slowly developing bacterial resistance, tropones and their derivatives hold great promise for biomedical or biotechnological applications, for instance as antibiotics in (shell)fish aquaculture.     

天然产物新分离技术的研究进展

综述天然产物提取分离的各种新技术、新方法,阐明了各种技术目前存在的主要问题及今后研究方向,为天然产物的开发利用提供参考,为新药开发和中药现代化献计献策.     

大孔吸附树脂及其在天然产物研究中的应用

介绍了大孔吸附树脂的吸附原理及其在抗生素、天然产物、生化药物的分离纯化以及中成药的制备和质量控制中的应用。     

天然产物对酪氨酸酶抑制作用的研究进展

随着酪氨酸酶抑制剂在美白型化妆品中的不断开发及应用,以及"纯天然化妆品"回归主流的趋势下,天然产物酪氨酸酶抑制剂的开发研究越来越得到重视。文章就天然产物在酪氨酸酶抑制剂方面的研究进展进行了论述,为酪氨酸酶天然抑制剂在化妆品等领域的研究及开发提出未来发展思路。     

Potential of Bacterial Cellulose Chemisorbed with Anti-Metabolites, 3-Bromopyruvate or Sertraline,to Fight against Helicobacter pylori Lawn Biofilm

Helicobacter pylori is a bacterium known mainly of its ability to cause persistent inflammations of the human stomach, resulting in peptic ulcer diseases and gastric cancers. Continuous exposure of this bacterium to antibiotics has resulted in high detection of multidrug-resistant strains and difficulties in obtaining a therapeutic effect. The purpose of the present study was to determine the usability of bacterial cellulose (BC) chemisorbed with 3-bromopyruvate (3-BP) or sertraline (SER) to act against lawn H. pylori biofilms. The characterization of BC carriers was made using a N2 adsorption/desorption analysis, tensile strength test, and scanning electron microscopy (SEM) observations. Determination of an antimicrobial activity was performed using a modified disk-diffusion method and a self-designed method of testing antibacterial activity against biofilm microbial forms. In addition, bacterial morphology was checked by SEM. It was found that BC disks were characterized by a high cross-linking and shear/stretch resistance. Growth inhibition zones for BC disks chemisorbed with 2 mg of SER or 3-BP were equal to 26.5–27.5 mm and 27–30 mm, respectively. The viability of lawn biofilm H. pylori cells after a 4-h incubation with 2 mg SER or 3-BP chemisorbed on BC disks was ≥4 log lower, suggesting their antibacterial effect. SEM observations showed a number of morphostructural changes in H. pylori cells exposed to these substances. Concluding, SER and 3-BP chemisorbed on BC carriers presented a promising antibacterial activity against biofilm H. pylori cells in in vitro conditions.     

分子蒸馏技术在天然产物分离与提纯方面的应用

分子蒸馏是一种新型的分离手段 ,具有蒸馏温度低、受热时间短、分离程度高等优点 ,在天然产物的分离与提纯方面有重要应用 ,文中对分子蒸馏技术的基本原理、在天然产物和植物药有效成分的分离和提纯中的最新应用进行了综述。     

天然产物纯度鉴定方法

天然产物产量小和结构复杂的特点,决定了其在进行结构研究之前,必须要确定化合物纯度。文章通过讨论熔点（mp）、薄层层析（TLC）、纸层析（PC）、气相色谱（GC）、高效滚相色谱（HPLC）、氢核磁共振（IHNMR）和碳核磁共振（13CNMR）的在纯度鉴定方面的特点。文章说明每一种鉴定方法有其优点,也有其不足之处,在研究过程中为了证明某个化合物纯度到达测试要求,要多试验几种纯度鉴定方法。     

生物活性天然产物分离技术的研究进展(英文)

Bioactive natural products are a main source of new drugs, functional foods and food additives. The separation of bioactive natural products plays an important role in transformation and use of biomass. The isolation and purification of bioactive_principle from a complex matrix is often inherent bottleneck for the utilization of natural products, so a series of extraction and separation techniques have been developed. This review covers recent advances in the separation of bioactive natural products with an emphasis on their solubility and diffusion coefficients, recent extraction techniques and isolation techniques. This overview of recent technological advances, dis- cussion of pertinent problems and prospect of current methodologies in the separation of bioactive natural products may provide a driving force for development of novel separation techniques.     

Aryl Polyenes,a Highly Abundant Class of Bacterial Natural Products,Are Functionally Related to Antioxidative Carotenoids

Bacterial pigments of the aryl polyene type are structurally similar to the well‐known carotenoids with respect to their polyene systems. Their biosynthetic gene cluster is widespread in taxonomically distant bacteria, and four classes of such pigments have been found. Here we report the structure elucidation of the aryl polyene/dialkylresorcinol hybrid pigments of Variovorax paradoxus B4 by HPLC‐UV‐MS, MALDI‐MS and NMR. Furthermore, we show for the first time that this pigment class protects the bacterium from reactive oxygen species, similarly to what is known for carotenoids. An analysis of the distribution of biosynthetic genes for aryl polyenes and carotenoids in bacterial genomes is presented; it shows a complementary distribution of these protective pigments in bacteria.     

天然产物是农药新型活性结构的重要先导库

综述了以天然产物为先导化合物研发农药的概况。     

Gold-Catalyzed Polycyclization Toward Natural Products Synthesis

Over the last years, gold catalysis has gained considerable significance in organic synthesis, since it allows atom economy and synthetic efficiency for the transformation of relatively simple substrates into valuable, highly complex molecular architectures. The gold-catalyzed polycyclization reactions of alkynes and enynes have been particularly successful toward the synthesis of natural products. This review highlights the recent developments in polycyclization area according to the key gold-catalyzed step.     

Natural Products with Activity against Lung Cancer: A Review Focusing on the Tumor Microenvironment

Lung cancer is one of the most prevalent malignancies worldwide. Despite the undeniable progress in lung cancer research made over the past decade, it is still the leading cause of cancer-related deaths and continues to challenge scientists and researchers engaged in searching for therapeutics and drugs. The tumor microenvironment (TME) is recognized as one of the major hallmarks of epithelial cancers, including the majority of lung cancers, and is associated with tumorigenesis, progression, invasion, and metastasis. Targeting of the TME has received increasing attention in recent years. Natural products have historically made substantial contributions to pharmacotherapy, especially for cancer. In this review, we emphasize the role of the TME and summarize the experimental proof demonstrating the antitumor effects and underlying mechanisms of natural products that target the TME. We also review the effects of natural products used in combination with anticancer agents. Moreover, we highlight nanotechnology and other materials used to enhance the effects of natural products. Overall, our hope is that this review of these natural products will encourage more thoughts and ideas on therapeutic development to benefit lung cancer patients.