中国南海软体动物及其食源生物的化学、化学生态学和生物活性研究

海洋软体动物色彩艳丽、行动缓慢,主要依赖次生代谢产物形成的化学防御机制对抗天敌的捕食.多数软体动物可以通过选择适当的食物并将其中有用的代谢物质经过进一步的生物转化或积累到身体的特定部位而用作化学防御物质,以保护自己不受天敌的捕食;少数软体动物能够生物合成自身所需要的化学物质,从而建立起化学防御体系.研究软体动物及其食源生物的化学组成可以揭示它们之间的食物链关系,并进一步阐明这些化学物质的生态学作用.同时,这种进化的化学防御体系也能为我们提供一种从自然界寻找生物活性物质的新方法.近年来,我们研究小组对中国南海软体动物及其相关食源生物海绵、珊瑚和海藻等常见海洋生物物种之间的食物链关系进行了系统研究,获得了这些海洋生物的化学及生物学等方面的知识,并对这些化学物质的药理活性进行了系统考察,为更加系统、深入地开展中国海洋天然产物研究、开发具有自主知识产权的海洋新药打下了坚实的基础.     

海洋药物—生态功能及其应用于海洋生物药研究的展望

海洋存在大量的生物多样性品种,以往人类主要从海洋生物资源中获得蛋白质,近年来,天然产物化学家开始从大量的海洋无脊椎动物如海绵,被囊动物,苔藓虫类及其其它如海藻等发现生物活性次生代谢产物,多种该类化合物具有强生物活性如抗肿瘤并已应用于临床研究,部分化合物则具有保护植物,（如天然杀虫剂）和作为天然化妆品配方的功能,本报告将报道具有新药开发前景的海洋天然产物的发展动态。在海洋中,生物活性分子通常作为化学保护以对抗环境的不利因素如被鱼软体动物吞噬,或竞争生存空间,本文将讨论从海绵中分到的天然产物的对鱼类的强拒食活性,众所周知,海洋无脊椎动物通常于各种海洋微生物包括细胞菌,真菌或微藻共生,这些微生物可能存在于细胞外,细胞内或存在于宿主细胞的核内,从结构特征看,海洋微生物可能参加了海洋无脊椎动物的代谢过程,因此,海洋天然产物化学家开始热衷于微生物天然产物－新药研究先导化合物的新资源的研究。     

海洋抗肿瘤药物研究

海洋是生命的起源地,占地球表面积的７０％、体积的９０％以上,不但蕴藏着大量丰富的矿产和能源,也包含着地球上８０％以上的生物资源。由于压力、盐分、温度和地质形态的相对变化,海洋中的生物种群复杂多样、种类繁多;它们通过食物链、化学信息、化学进攻和防御等机制相互依存、相互独立,维系着独特、紧密的海洋生物生态体系。为了生存,海洋生物代谢产生许多具有特殊作用的生理活性物质,是人类与疾病斗争可利用的重要药物资源。有人讲下一世纪是海洋药物的世纪,不论这种说法是否准确,但可以肯定人们研究较少的巨大海洋生物资源在…     

海洋药物研究进展

海洋是一个巨大的天然产物宝库。占地球面积 71%的海洋中生活着约 40万种生物 ,占地球生物物种的 80 %。生长在海洋这—特殊环境 (高盐、高压、缺氧、缺少光照等 )中的海洋生物 ,在其生长和代谢过程中 ,产生并积累了大量具有特殊化学结构并具特殊生理活性和功能的物质 ,是开发新型海洋药物和功能食品的重要资源。目前开发利用海洋生物资源已成为世界各国竞相研究的一个重要领域和发展方向。研究开发海洋天然产物 (海洋药物、功能食品、生物材料等 )对充分利用我国丰富的海洋资源 ,提高科学技术水平 ,发展国民经济都具有重要的战略意义。世界…     

海洋药物——二十一世纪中国药学研究的新热点

海洋是生命之源 ,海洋生物活性物质主要包括生物信息物质、各类活性成分、海生毒素、生物功能材料等 ,研究海洋生物活性物质是海药研究的主导方向。近年来 ,国际上出现大量涉及药学、食品、功能食品、化妆品、酶制剂、生物工具药方面的海洋天然产物专利产品 ,发现一大批高效的抗菌、抗病毒、抗炎、抗肿瘤、镇痛、防治心脑血管疾病的海洋生物活性物质 ,多数化合物具有新药开发潜力。但与来源于陆生植物的 1 5万多种天然产物相比 ,海洋天然产物至今才 1万多种 ,从资源研究上看 ,目前用于研究的海洋生物仅几千种 ,表明海洋生物具有巨大潜力等待…     

海洋功能食品的研究开发（一）

海洋是一个巨大的天然产物宝库,开发利用这个天然宝库已成为当今世界科学研究的焦点。利用海洋生物开发海洋功能食品,是功能食品研究中具有巨大开发潜力的一部分。生长在海洋这一特殊环境中的海洋生物,在其生长和代谢过程中,产生并积累了大量具有特殊化学结构,并具有特殊生理活性和功能的物质。海洋生物是开发新型海洋药物和功能食品的重要资源。     

化学表观遗传修饰方法在真菌次级代谢产物研究中的应用

真菌产生的次级代谢产物是新药开发的重要资源,其生物合成过程受到众多因素的调控。化学表观遗传操作是利用小分子化学物质抑制真菌中影响表观遗传的酶类,激活沉默的生物合成基因,诱导真菌产生未知的次级代谢产物。化学表观遗传修饰已成为一种简单有效的发现结构新颖的活性次级代谢产物的新方法。本文综述了化学表观遗传修饰调控真菌次级代谢产物的研究进展,并对该方法用于海洋来源真菌次级代谢产物的研究进行了展望。     

海洋天然活性物质心血管药理作用的研究进展

从30多年来国内外学者在海洋生物天然活性物质的研究中，对具心血管药理作用的活性产物作系统、概括的报道。从1968年以来获得的55种海洋生物活性物质，对每一种天然产物分别概括其来源、化学成分，并重点阐述其心血管方面的药理作用。系统报道这些海洋天然活性物质的研究成果及进展，对进一步开展海洋心血管药物的研发提供参考。     

具有抗真菌活性的海洋天然产物研究进展

海洋是世界上最大的生物资源宝库。由于海洋生态系统的特殊性(高压、高盐、低氧)给海洋生物之间的生存带来了非常激烈的竞争，导致很多海洋生物在其生命活动中产生了具有大量特殊结构和生物活性的次生代谢产物。本文总结了2016—2021年从海洋来源的微生物、动物、植物中提取的93个天然的抗真菌活性物质，并对它们的应用前景进行了展望。同时，还总结了这些海洋天然产物的抗真菌作用。     

海洋生物活性物质研究进展

进入2l世纪以来，海洋药物从研究方法、基础理论到生产应用的研究日趋深入，多种海洋天然产物已进入临床试验阶段。海洋生物由于其独特的代谢方式，产生的活性物质化学结构丰富多样，分子结构独特新颖具有极大的药用潜力，从海洋中寻找生物活性物质并开发研究新的药物前景广阔。现简述2l世纪海洋生物活性物质研究进展。     

Diet Diversity in Carnivorous Terebrid Snails Is Tied to the Presence and Absence of a Venom Gland

Predator-prey interactions are thought to play a driving role in animal evolution, especially for groups that have developed venom as their predatory strategy. However, how the diet of venomous animals influences the composition of venom arsenals remains uncertain. Two prevailing hypotheses to explain the relationship between diet and venom composition focus on prey preference and the types of compounds in venom, and a positive correlation between dietary breadth and the number of compounds in venom. Here, we examined venom complexity, phylogenetic relationship, collection depth, and biogeography of the Terebridae (auger snails) to determine if repeated innovations in terebrid foregut anatomy and venom composition correspond to diet variation. We performed the first molecular study of the diet of terebrid marine snails by metabarcoding the gut content of 71 terebrid specimens from 17 species. Our results suggest that the presence or absence of a venom gland is strongly correlated with dietary breadth. Specifically, terebrid species without a venom gland displayed greater diversity in their diet. Additionally, we propose a revision of the definition of venom complexity in conoidean snails to more accurately capture the breadth of ecological influences. These findings suggest that prey diet is an important factor in terebrid venom evolution and diversification and further investigations of other understudied organisms, like terebrids, are needed to develop robust hypotheses in this area.     

Marine natural products influencing larval settlement and metamorphosis of marine sessile organisms]

Most marine sessile organisms have a planktonic larval phase in their life cycles, and then larvae settle and metamorphose into their adult forms. The selection of settlement sites is a critical event for these organisms because settlement on unsuitable places affects their survivorship severely. Ascidians live gregariously, and conspecific chemical cues are thought to play an important role in gregarious settlement of larvae. The extracts of conspecific adults or larvae have been claimed to contain "natural metamorphosis inducers." Little is known, however, about their chemical properties. To discover natural signal substances for larval metamorphosis in ascidians, we surveyed the metamorphosis-inducing activity of the medium conditioned by ascidian larvae, and succeeded in isolating a metamorphosis-inducing substance from the conditioned medium of Halocycthia roretzi larvae and found that it was identical to lumichrome. We have also isolated more than 40 active metabolites, which may mimic lumichrome, from marine sponges. On the contrary, marine sessile organisms cause serious problems by settling on fishing nets, hulls of ships, and cooling systems of power plants. Organotin compounds have been widely used for the control of these organisms, but they are known to be toxic to marine biota. Therefore, nontoxic antifouling substances are urgently needed. Marine sessile organisms possess chemical defense systems using their secondary metabolites, which might be potential by nontoxic antifouling agents. We have attempted to obtain antibarnacle substances from marine sponges and isolated 26 antifoulants.     

南海海绵的结构多样性和生物活性

海绵是重要的海洋生物资源,由于其生态条件特殊,产生的天然产物结构多样、生物活性显著。本文就作者近年对我国南海海绵代谢产物及其生物活性研究的部分结果进行总结,以阐明我国海绵生物资源的结构多样性,为我国海绵作为药用资源的深入研究提供参考依据。     

天然产物的结构改造

药理活性和成药性是新药创制的两大要素, 药理活性自不待言, 成药性是由分子的物理化学性质、生物化学性质、药代动力学性质和安全性所支撑。天然产物作为动物、植物、微生物和海洋生物的次级代谢产物, 具有维持生理、自身防御和种群繁衍的功能, 许多药物来自天然产物。天然产物具有多样性和复杂性结构, 多含立体化学中心, 氮和卤素含量低。天然活性物质是良好的先导物, 但未必能满足成药性要求, 需要进行结构修饰和优化。结构改造的要旨是: 根据天然产物的分子大小和复杂程度, 采取不同的化学处置方式, 复杂和较大的分子作结构剖裂, 去除冗余原子; 研究构效关系, 提取药效团, 实现骨架迁越, 获得新结构类型分子; 消除不必要的手性中心, 保留与靶标结合的必须的构型与构象; 全合成实现工业化, 保护环境与资源。天然产物结构改造的方略是: 提高活性强度和选择性作用; 改善物理化学性质; 提高化学和代谢稳定性; 改善生物化学性质; 改善药代动力学性质; 消除或降低毒副作用和不良反应; 获得知识产权。本文以成功的实例解析以天然活性物质为先导物研制新药的内涵。     

Natural marine anti-inflammatory products

The marine environment has been shown to be the source of a great diversity of chemical structures with promising biological activities. The isolation, biological evaluation, chemical properties and synthetic elaborations of the products of marine organisms and microorganisms have attracted the attention of organic chemists, medicinal chemists, biologists and pharmacists. Marine organisms and microorganisms have provided a large proportion of the natural anti-inflammatory products over the last years. Marine organisms include green algae, brown algae, red algae, sponges, coelenterates, bryozoans, molluscs, tunicates, echinoderms, miscellaneous marine organisms and marine microorganisms and phytoplankton. This review describes current progress in the development of a selection of new anti-inflammatory agents from marine sources. The chemistry and biological evaluation are discussed.     

Production of toxic metabolites in Aspergillus niger, Aspergillus oryzae, and Trichoderma reesei: justification of mycotoxin testing in food grade enzyme preparations derived from the three fungi

Aspergillus niger, Aspergillus oryzae, and Trichoderma reesei are three important production organisms used in industrial fermentations. Several of the fungal secondary metabolites produced by selected strains of these three fungi are capable of eliciting toxicity in animals. Among those toxic substances are the well-known mycotoxins 3-nitropropionic acid and ochratoxin A. However, many others, such as kojic acid, may not be true mycotoxins. The production, extraction, chemical structure, and the toxicity (expressed as LD(50)) of these substances are reviewed. Production of toxic secondary metabolites in A. niger, A. oryzae, and T. reesei is strain-specific and environment-dependent. Considering all of the safety measures taken in the industrial production process, these three fungal species are safe to use. The recently revised JECFA specification for mycotoxins in food enzyme preparations is also discussed. The extent of mycotoxin tests in food enzyme preparations should be judged on a case-by-case basis, through a careful evaluation based on knowledge of taxonomy, biochemistry, and genetics. In many cases, the testing scope at the level of genus should be sufficient. In other cases, the scope can even be further narrowed based on scientific knowledge and assessment.     

Chemical diversity of bioactive marine natural products: an illustrative case study

The marine environment contains a number of plants, animals and micro organisms, which, due to the unique adaptations to their habitat, elaborate a wide diversity of natural products with specific bioactivities. These products provide a rich source of chemical diversity that can be used to design and develop new potentially useful therapeutic agents. The huge variety of the structures present in marine organisms has been illustrated through the case study of the sponge Plakortis simplex, whose chemical analysis, started in our laboratories about ten years ago, revealed an incredible variety and abundance of secondary metabolites. The obtained results have been presented with the intention of drawing some conclusions of general relevance. Particularly, the problem of the limited availability of natural compounds for both structural and preliminary pharmacological studies has been discussed, this issue becoming a serious obstacle when the pharmacological research reaches a more advanced stage. Furthermore, the origin of the chemodiversity in Plakortis simplex and, in general, in marine invertebrates has been discussed; in this respect, the possible cooperative role of symbiotic micro-organisms in the biosynthesis of the varied metabolic content typical of these organisms has been considered.     

Drug discovery from natural sources

Organic compounds from terrestrial and marine organisms have extensive past and present use in the treatment of many diseases and serve as compounds of interest both in their natural form and as templates for synthetic modification. Over 20 new drugs launched on the market between 2000 and 2005, originating from terrestrial plants, terrestrial microorganisms, marine organisms, and terrestrial vertebrates and invertebrates, are described. These approved substances, representative of very wide chemical diversity, together with several other natural products or their analogs undergoing clinical trials, continue to demonstrate the importance of compounds from natural sources in modern drug discovery efforts.     

Secondary metabolites from the South China Sea invertebrates: chemistry and biological activity

The increasing demand for new lead compounds in the pharmaceutical and agrochemical industries has driven scientists to search for new sources of bioactive natural products. Marine invertebrates are a rich source of novel, bioactive secondary metabolites and they have attracted a great deal of attention from scientists in the fields of chemistry, pharmacology, ecology, and molecular biology. During the past 25 years, many complex and structurally unique secondary metabolites have been isolated from the invertebrates inhabiting the South China Sea. These metabolites are responsible for various bioactivities such as anti-tumor, anti-inflammation and antioxidant activities, and/or they act on the cardiovascular system. This review will focus on the marine natural product chemistry of invertebrates from the South China Sea, aiming to give the reader a brief view of the compounds isolated from these invertebrates, as well as their biological activities. The article covers the literature published during the period from the beginning of 1980 to the end of 2005, with 340 citations and 811 compounds from invertebrates from the South China Sea, including sponges, coelenterates, molluscs and echinoderms.