Chemical defenses: from compounds to communities

Marine natural products play critical roles in the chemical defense of many marine organisms and in some cases can influence the community structure of entire ecosystems. Although many marine natural products have been studied for biomedical activity, yielding important information about their biochemical effects and mechanisms of action, much less is known about ecological functions. The way in which marine consumers perceive chemical defenses can influence their health and survival and determine whether some natural products persist through a food chain. This article focuses on selected marine natural products, including okadaic acid, brevetoxins, lyngbyatoxin A, caulerpenyne, bryostatins, and isocyano terpenes, and examines their biosynthesis (sometimes by symbiotic microorganisms), mechanisms of action, and biological and ecological activity. We selected these compounds because their impacts on marine organisms and communities are some of the best-studied among marine natural products. We discuss the effects of these compounds on consumer behavior and physiology, with an emphasis on neuroecology. In addition to mediating a variety of trophic interactions, these compounds may be responsible for community-scale ecological impacts of chemically defended organisms, such as shifts in benthic and pelagic community composition. Our examples include harmful algal blooms; the invasion of the Mediterranean by Caulerpa taxifolia; overgrowth of coral reefs by chemically rich macroalgae and cyanobacteria; and invertebrate chemical defenses, including the role of microbial symbionts in compound production.     

Structural analogues of schweinfurthin F: Probing the steric,electronic, and hydrophobic properties of the D-ring substructure

The natural tetracyclic schweinfurthins are potent and selective inhibitors of cell growth in the National Cancer Institute’s 60-cell line screen. An interest in determination of their cellular or molecular target has inspired our efforts to prepare both the natural products and analogues. In this paper, chemical synthesis of analogues modified in different olefinic positions, and preliminary results from studies of their biological activity, are reported.     

Marine Natural Products: The Important Resource of Biological Insecticide

Due to the unique environmental conditions and vast territory, marine habitat breeds more abundant biological resources than terrestrial environment. Massive marine biological species provide valuable resources for obtaining a large number of natural products with diverse structure and excellent activity. In recent years, new breakthroughs have been made in the application of marine natural products in drug development. In addition, the use of marine natural products to develop insecticides and other pesticide products has also been widely concerned. Targeting marine plants, animals, and microorganisms, we have collected information on marine natural products with insecticidal activity for nearly decade, including alkaloids, terpenes, flavonoids and phenols fatty acids, peptides, and proteins, et al. In addition, some active crude extracts are also included. This review describes the insecticidal activities of marine natural products and their broad applications for future research in agriculture and health.     

源于海洋真菌的抗肿瘤天然产物

海洋真菌因其特殊的生存环境和代谢机制而具有产生新型生物活性物质的潜力。近年来随着对海洋微生物研究的深入,从海洋真菌中发现了越来越多的具有抗肿瘤活性且结构新颖的天然产物。这些海洋真菌有的分离自海水、海泥或海洋沉积物,有的来自于海洋生物体。本文综述了近几年来从海洋真菌中分离得到的抗肿瘤天然产物的研究状况。     

Drug Discovery from Marine Microbes

The marine environment has been a source of more than 20,000 inspirational natural products discovered over the past 50 years. From these efforts, 9 approved drugs and 12 current clinical trial agents have been discovered, either as natural products or as molecules inspired from the natural product structure. To a significant degree, these have come from collections of marine invertebrates largely obtained from shallow-water tropical ecosystems. However, there is a growing recognition that marine invertebrates are oftentimes populated with enormous quantities of “associated” or symbiotic microorganisms and that microorganisms are the true metabolic sources of these most valuable of marine natural products. Also, because of the inherently multidisciplinary nature of this field, a high degree of innovation is characteristic of marine natural product drug discovery efforts.     

海洋药物的抗病毒研究

海洋由于其特殊的生态环境,包含着极其丰富的生物来源的天然产物。自本世纪七十年代以来,已经从海藻类、海绵类、海鞘类、海星类、腹足动物、棘皮动物、腔肠动物、软体动物、珊瑚及海洋微生物等海洋生物中分离出一系列有抗病毒作用的天然化合物,其中有些结构类型已成为抗病毒药物研究的导向化合物。基于现代分离和分析技术的发展、新的实验模型的建立和在病毒学方面分子生物学研究的进展,从海洋生物中寻找新的抗病毒药物已步入一个新的时代。     

化学生态学在海洋污损生物防除中的应用

在海洋环境中,许多海洋生物都能产生对环境无危害的、具有防污活性的次生代谢产物以保护自身的洁净,利于自身的生存.用化学生态学的方法从海洋生物中提取天然防除物质成为近年来解决海洋污损生物问题的新思路,其目标是寻找高效无毒的防污材料取代原有的对海洋环境有严重危害的化学合成防污材料.虽然目前对提取生物的次生代谢产物的防污机理还所知甚少,但不少从海洋生物中获得的天然产物已显示出良好的防污活性.要解决污损生物防污问题,还需对天然产物的作用机制、生态学效应、天然产物与涂料的结合、控制和释放及野外实验进行更加深入的研究与探讨.     

Bio-mining the microbial treasures of the ocean: new natural products

The biological resources of the oceans have been exploited since ancient human history, mainly by catching fish and harvesting algae. Research on natural products with special emphasis on marine animals and also algae during the last decades of the 20th century has revealed the importance of marine organisms as producers of substances useful for the treatment of human diseases. Though a large number of bioactive substances have been identified, some many years ago, only recently the first drugs from the oceans were approved. Quite astonishingly, the immense diversity of microbes in the marine environments and their almost untouched capacity to produce natural products and therefore the importance of microbes for marine biotechnology was realized on a broad basis by the scientific communities only recently. This has strengthened worldwide research activities dealing with the exploration of marine microorganisms for biotechnological applications, which comprise the production of bioactive compounds for pharmaceutical use, as well as the development of other valuable products, such as enzymes, nutraceuticals and cosmetics. While the focus in these fields was mainly on marine bacteria, also marine fungi now receive growing attention. Although culture-dependent studies continue to provide interesting new chemical structures with biological activities at a high rate and represent highly promising approaches for the search of new drugs, exploration and use of genomic and metagenomic resources are considered to further increase this potential. Many efforts are made for the sustainable exploration of marine microbial resources. Large culture collections specifically of marine bacteria and marine fungi are available. Compound libraries of marine natural products, even of highly purified substances, were established. The expectations into the commercial exploitation of marine microbial resources has given rise to numerous institutions worldwide, basic research facilities as well as companies. In Europe, recent activities have initiated a dynamic development in marine biotechnology, though concentrated efforts on marine natural product research are rare. One of these activities is represented by the Kieler Wirkstoff-Zentrum KiWiZ, which was founded in 2005 in Kiel (Germany).     

Photosynthetic marine organisms as a source of anticancer compounds

Since early human history, plants have served as the most important source of medicinal natural products, and even in the “synthetic age” the majority of lead compounds for pharmaceutical development remain of plant origin. In the marine realm, algae and seagrasses were amongst the first organisms investigated by marine natural products scientists on their quest for novel pharmaceutical compounds. Forty years after the pioneering work in the field of marine drug discovery began, the biodiversity of marine organisms investigated as potential sources of anticancer, anti-inflammatory, and antibiotic compounds has increased tremendously. Nonetheless, marine plants are still an important source of novel secondary metabolites with interesting biomedical properties. The present review focuses on the antitumour properties of compounds isolated from marine algae, phytoplankton, mangroves, seagrasses, or cordgrasses. Compounds produced by marine epi- or endophytic fungi are also discussed.     

甜菊苷及其衍生物的生物活性研究进展

甜菊苷是一种常用天然甜味剂,属于四环二萜糖苷类。药理学研究表明,甜菊苷及其水解产物甜菊醇、异甜菊醇和甜菊双糖苷等具有降血糖、降血压、抗炎、抗肿瘤、止泻、抗菌和免疫调节等多种生物活性。综述甜菊苷、甜菊醇、异甜菊醇、甜菊双糖苷及相关衍生物的生物活性研究进展。     

Zebrafish Embryo Toxicity Microscale Model for Ichthyotoxicity Evaluation of Marine Natural Products

Marine organisms often protect themselves against their predators by chemical defensive strategy. The second metabolites isolated from marine organisms and their symbiotic microbes have been proven to play a vital role in marine chemical ecology, such as ichthyotoxicity, allelopathy, and antifouling. It is well known that the microscale models for marine chemoecology assessment are urgently needed for trace quantity of marine natural products. Zebrafish model has been widely used as a microscale model in the fields of environment ecological evaluation and drug safety evaluation, but seldom reported for marine chemoecology assessment. In this work, zebrafish embryo toxicity microscale model was established for ichthyotoxicity evaluation of marine natural products by using 24-well microplate based on zebrafish embryo. Ichthyotoxicity was evaluated by observation of multiple toxicological endpoints, including coagulation egg, death, abnormal heartbeat, no spontaneous movement, delayed hatch, and malformation of the different organs during zebrafish embryogenesis periods at 24, 48, and 72 h post-fertilization (hpf). 3,4-Dichloroaniline was used as the positive control for method validation. Subsequently, the established model was applied to test the ichthyotoxic activity of the compounds isolated from corals and their symbiotic microbes and to isolate the bioactive secondary metabolites from the gorgonian Subergorgia mollis under bioassay guidance. It was suggested that zebrafish embryo toxicity microscale model is suitable for bioassay-guided isolation and preliminary bioactivity screening of marine natural products.     

Marine drugs--macrolactins

The increasing demands for new lead compounds in pharmaceutical and agrochemical industries have driven scientists to search for new bioactive natural products. Marine microorganisms are rich sources of novel, bioactive secondary metabolites, and have attracted much attention of chemists, pharmacologists, and molecular biologists. This mini-review mainly focuses on macrolactins, a group of 24-membered lactone marine natural products, aiming at giving an overview on their sources, structures, biological activities, as well as their potential medical applications.     

海洋真菌抗污损活性天然产物研究

黏附于海洋船舶或人工设施表面的污损生物给人类海洋生产活动与生态环境带来诸多不利影响.将具有抗污损活性的化合物开发成防污涂料是目前防治海洋生物污损的最常用手段之一.而大量传统有机金属防污剂因其严重毒副作用被禁用,亟须开发高效、环境友好型抗污损涂料.海洋真菌能够产生大量结构新颖、作用机制独特的高效、低毒/无毒抗污损活性次级...     

海鞘类天然产物的最新研究进展

近年来,从海洋生物海鞘中分离出很多结构新颖而又有显著生理活性的天然化合物,引起了有机化学家和药学家的关注。本文综述了国内外最近几年对海鞘类天然产物的研究进展,并按化学结构类型进行了分类。     

Bioactive Pimarane‐Type Diterpenes from Marine Organisms

Marine organisms represent an abundant sources of bioactive natural products with unique chemical structure. Pimarane diterpenes are a structurally diverse family of natural products with various biological activities and pharmacological properties. A prolific source of new marine‐derived pimarane diterpenes have attracted considerable interest because of their unique structural diversity and varied biological activities, including antimicrobial, antitumor, and antiproliferative activities. This review provides a comprehensive overview of the structures, names, bioactivities, and references of 80 marine‐derived pimarane‐type natural products for the first time.     

Indole alkaloid marine natural products: an established source of cancer drug leads with considerable promise for the control of parasitic, neurological and other diseases

The marine environment produces natural products from a variety of structural classes exhibiting activity against numerous disease targets. Historically marine natural products have largely been explored as anticancer agents. The indole alkaloids are a class of marine natural products that show unique promise in the development of new drug leads. This report reviews the literature on indole alkaloids of marine origin and also highlights our own research. Specific biological activities of indole alkaloids presented here include: cytotoxicity, antiviral, antiparasitic, anti-inflammatory, serotonin antagonism, Ca-releasing, calmodulin antagonism, and other pharmacological activities.     

海洋真菌生物活性物质研究之管见

海洋真菌是活性海洋天然产物的重要来源,到目前为止,已从海洋真菌的发酵产物中分离鉴定了1,117个新化合物。介绍了海洋真菌次生代谢产物的研究历史、现状、特点、研究方法、存在问题及其在新药研究中的应用前景。     

Molluscan biological and chemical diversity: secondary metabolites and medicinal resources produced by marine molluscs

The phylum Mollusca represents an enormous diversity of species with eight distinct classes. This review provides a taxonomic breakdown of the published research on marine molluscan natural products and the medicinal products currently derived from molluscs, in order to identify priority targets and strategies for future research. Some marine gastropods and bivalves have been of great interest to natural products chemists, yielding a diversity of chemical classes and several drug leads currently in clinical trials. Molluscs also feature prominently in a broad range of traditional natural medicines, although the active ingredients in the taxa involved are typically unknown. Overall secondary metabolites have only been investigated from a tiny proportion (<1%) of molluscan species. At the class level, the number of species subject to chemical studies mirrors species richness and our relative knowledge of the biology of different taxa. The majority of molluscan natural products research is focused within one of the major groups of gastropods, the opisthobranchs (a subgroup of Heterobranchia), which are primarily comprised of soft‐bodied marine molluscs. Conversely, most molluscan medicines are derived from shelled gastropods and bivalves. The complete disregard for several minor classes of molluscs is unjustified based on their evolutionary history and unique life styles, which may have led to novel pathways for secondary metabolism. The Polyplacophora, in particular, have been identified as worthy of future investigation given their use in traditional South African medicines and their abundance in littoral ecosystems. As bioactive compounds are not always constitutively expressed in molluscs, future research should be targeted towards biosynthetic organs and inducible defence reactions for specific medicinal applications. Given the lack of an acquired immune system, the use of bioactive secondary metabolites is likely to be ubiquitous throughout the Mollusca and broadening the search field may uncover interesting novel chemistry.     

Bioactive Compounds from Marine Bacteria and Fungi

Marine bacteria and fungi are of considerable importance as new promising sources of a huge number of biologically active products. Some of these marine species live in a stressful habitat, under cold, lightless and high pressure conditions. Surprisingly, a large number of species with high diversity survive under such conditions and produce fascinating and structurally complex natural products. Up till now, only a small number of microorganisms have been investigated for bioactive metabolites, yet a huge number of active substances with some of them featuring unique structural skeletons have been isolated. This review covers new biologically active natural products published recently (2007–09) and highlights the chemical potential of marine microorganisms, with focus on bioactive products as well as on their mechanisms of action.     

Some results and prospects of studies in the area of marine biochemistry and biotechnology]

Recent studies on bioactive metabolites from marine macro- and microorganisms are reviewed with 83 refs. Structures of new sulphated and glycosylated secondary metabolites, which have been reported to have antifungal, immunomodulatory, and cytotoxic properties, are given. Some peculiarities of biosynthesis of natural compounds in marine organisms are revealed. It was shown that some natural products, isolated earlier from sponges, are produced by microbial symbionts. Different physiological activities associated with 8000 marine microbial (mainly symbiotic) strains are discussed as well as some prospects of marine biochemistry and biotechnology development.