民族药标本资源共享平台及在生物多样性保护领域的应用展望(下)(英文)

<正>APPLICATION PROSPECT OF SPESR IN BIODIVERSITY PROJECT 1 Introduction of the International Cooperative Biodiversity Groups(ICBG) Program ICBG program is a unique effort that addresses the interde- pendent issues of drug discovery,biodiversity conservation,and sustainable economic growth.The FIC-managed Biodiversity Pro-     

Reporter gene assays and their applications to bioassays of natural products

Medicinal plants represent precious resources from which bioactive compounds can be isolated and developed into invaluable therapeutic agents. With the advent of modern drug discovery technologies such as combinatorial chemistry and high-throughput drug screening platforms, there is an increasing interest in utilizing medicinal plants as a source of drug leads. A wide spectrum of bioassays can be employed for the detection of bioactivity in extracts, fractions, as well as purified compounds of herbal origin. Amongst the different types of bioassays, reporter gene assays are highly versatile and reliable. The present review provides an overview of the most popular reporter genes in terms of their basic methodology, capacities and limitations. The different types of intracellular and extracellular reporter gene products and their potential applications in bioassays of natural products are also discussed.     

The role of weeds as sources of pharmaceuticals

Primary tropical forest is generally considered to be the most likely habitat to discover new pharmaceuticals, due to high biodiversity and endemism. However, many indigenous groups rely on non-forested disturbed environments for medicinal plants. An ethnobotanical approach to drug discovery suggests that these disturbed environments may also harbor potentially useful medicinal compounds. Despite the neglect by current researchers to conduct drug discovery in disturbed environments, many source plants for modern pharmaceuticals thrive in disturbed areas. An analysis of the 101 plant species from which 119 contemporary pharmaceuticals are derived shows that at least 36 of these plants are considered weeds (Chi 2 = 343.34, P<0.0001). These results are an order of magnitude higher than what would be predicted by random occurrence of weeds in the modern pharmacopeia. Biochemical evidence based on literature is presented to explain this occurrence. This finding suggests that disturbed habitats may be important areas to search for novel compounds in drug discovery.     

Ethnomedicinal knowledge of indigenous communities and pharmaceutical potential of rainforest ecosystems in Fiji Islands

The World Health Organization recently raised concerns about antimicrobial resistance and lack of novel antibiotics in the health sector. The success rate of drug discovery is higher when chemical constituents are sourced from natural products and when drug candidates are based on the indigenous knowledge of local communities. Tropical rainforests are an important source of medicinal plants for traditional healthcare systems. The pharmaceutical industry also recognizes the potential of rainforests in novel drug development. However, habitat degradation and loss of traditional knowledge are endangering the healing powers of nature. The islands of Fiji have a rich cultural history of traditional medicine and a number of medicinal plants are sourced from the country’s rainforest ecosystems. While deforestation and forest degradation are decimating unique rainforest biodiversity and reducing access to medicinal plants in the wild, inter-generational erosion of ethnobotanical knowledge is attributed to acculturation, rural-urban migration and their effects on the transmission of oral traditions from one generation to another. Under these conditions, plants may disappear before their therapeutic value is formally identified. This review summarizes the importance of traditional medicinal knowledge and the potential for drug discovery from the tropical rainforest ecosystems of Fiji. However, there are several challenges that need to be addressed to realize the true potential of ethnopharmacology in this country.     

Developing a drug-like natural product library

Addressing drug-like/lead-like properties of biologically active small molecules early in a lead generation program is the current paradigm within the drug discovery community. Lipinski's "rule of five" has become the most commonly used tool to assess the relationship between structures and drug-like properties. Sixty percent of the 126 140 unique compounds in The Dictionary of Natural Products had no violations of Lipinski's "rule of five". We have isolated 814 natural products based on their expected drug-like/lead-like properties to generate a natural product library (NPL) in which 85% of the isolated compounds had no Lipinski violations. The library demonstrates the feasibility of obtaining natural products known for rich chemical diversity with the required physicochemical properties for drug discovery. The knowledge generated in creation of the library of structurally characterized pure natural products may provide opportunities to front-load lead-like property space in natural product drug discovery programs.     

High-throughput profiling of microbial extracts

Microbial culture extracts are used for natural products screening in the drug lead discovery process. An extract of a microbial culture is a complex mixture of organic compounds, making it difficult to evaluate the diversity and redundancy of the compounds. However, having a diverse extract library is a key to success in generating a lead for drug discovery. We have developed a high-throughput and robust LC-MS analysis and data processing method for visualizing sample profile and diversity. In the LC-MS analysis of 16?025 microbial culture extracts, positive and negative ions were acquired simultaneously with an electrospray ionization source. The raw data were processed using ACD IntelliXtract, and peak lists of each extract were generated and stored in the database. The peak list data were binned by nominal mass (m/z 150-1350) and retention time. How frequently the binned peaks, termed peak identifiers, appeared in the extracts library was calculated, and these data were visualized by scattered plots in Spotfire. From 4 to 115 peaks were observed in each sample. As it is easy to eliminate the ubiquitous peaks shown in most samples and simplify the plots, the unique or redundant compounds could be detected.     

Herbal compounds for rheumatoid arthritis: Literatures review and cheminformatics prediction

Rheumatoid arthritis (RA) is a systemic disease characterized by autoimmunity, joint inflammation, and cartilage destruction, which affects 0.5–1% of the population. Many compounds from herbal medicines show the potentials to treat RA. On this basis, the compounds with good pharmacokinetic behaviors and drug‐likeness properties will be further studied and developed. Therefore, the herbal compounds with anti‐RA activities were reviewed in this paper, and the cheminformatics tools were used to predict their drug‐likeness properties and pharmacokinetic parameters. A total of 90 herbal compounds were analyzed, which were reported to be effective on RA models through anti‐inflammation, chondroprotection, immunoregulation, antiangiogenesis, and antioxidation. Most of the herbal compounds have good drug‐likeness properties. Most of the compounds can be an alternative and valuable source for anti‐RA drug discovery.     

"Studies on biodiversity of Vietnam and Laos" 1998-2005: examining the impact

The impact of the University of Illinois at Chicago-based Vietnam-Laos International Cooperative Biodiversity Group (ICBG) Program "Studies on Biodiversity of Vietnam and Laos", which has been in operation for the period of 1998-2005, touches on five major areas of endeavor: (a) biodiversity inventory and conservation; (b) studies on medicinal plants; (c) drug discovery and development; (d) economic development; and (e) issues on intellectual property rights and benefit sharing in natural products drug discovery and development. Highlights are presented and the significance is discussed.     

The role of natural product chemistry in drug discovery

Although traditionally natural products have played an important role in drug discovery, in the past few years most Big Pharma companies have either terminated or considerably scaled down their natural product operations. This is despite a significant number of natural product-derived drugs being ranked in the top 35 worldwide selling ethical drugs in 2000, 2001, and 2002. There were 15 new natural product-derived drugs launched from 2000 to 2003, as well as 15 natural product-derived compounds in Phase III clinical trials or registration at the end of 2003. Recently, there has been a renewed interest in natural product research due to the failure of alternative drug discovery methods to deliver many lead compounds in key therapeutic areas such as immunosuppression, anti-infectives, and metabolic diseases. To continue to be competitive with other drug discovery methods, natural product research needs to continually improve the speed of the screening, isolation, and structure elucidation processes, as well addressing the suitability of screens for natural product extracts and dealing with issues involved with large-scale compound supply.     

Commentary: “A systems view on the future of medicine: Inspiration from Chinese medicine?”

Chinese medicine could serve as a source of inspiration for drug development. Using systems biology in combination with reverse pharmacology is a novel way for the discovery of novel biological active compounds and targets as well as for proving the occurrence of synergy and prodrugs. A key factor for coming to evidence-based Chinese medicine will be the quality control. Metabolomics is a very promising tool for this purpose.     

Neotropics and natural ingredients for pharmaceuticals: why isn't South American biodiversity on the crest of the wave?

Despite the advent of biotechnology and modern methods of combinatorial chemistry and rational drug design, nature still plays a surprisingly important role as a source of new pharmaceutical compounds. These are marketed either as herbal drugs or as single active ingredients. South American tropical ecosystems (or the Neotropics) encompass one‐third of the botanical biodiversity of the planet. For centuries, indigenous peoples have been using plants for healing purposes, and scientists are making considerable efforts in order to validate these uses from a pharmacological/phytochemical point of view. However, and despite the unique plant diversity in the region, very few natural pharmaceutical ingredients from this part of the world have reached the markets in industrialized countries. The present review addresses the importance of single active ingredients and herbal drugs from South American flora as natural ingredients for pharmaceuticals; it highlights the most relevant cases in terms of species of interest; and discusses the key entry barriers for these products in industrialized countries. It explores the reasons why, in spite of the region's competitive advantages, South American biodiversity has been a poor source of natural ingredients for the pharmaceutical industry. Copyright © 2010 John Wiley & Sons, Ltd.     

天然产物中的AMPK激活剂研究进展

单磷酸腺苷活化蛋白激酶(AMPK)被称为真核细胞的"能量感受调节器",是治疗高脂血症和糖尿病等代谢性疾病的药物靶点之一。天然产物种类繁多、结构多样,是药物发现的重要来源。按照天然产物的结构分类,综述了来源于天然产物的AMPK激活剂研究进展,为AMPK激活剂类药物的开发提供有益参考。     

天然药物化学史话:紫杉醇

癌症是威胁人类健康的第二大疾病,征服癌症是科学家们的一大梦想。天然产物一直是发现新药和药物先导化合物的重要途径之一,很多抗癌药物都是直接或间接来源于天然产物。紫杉醇是目前已发现的最优秀的天然抗癌药物,在临床上已经广泛用于乳腺癌、卵巢癌和部分头颈癌和肺癌的治疗。紫杉醇作为一个具有抗癌活性的二萜生物碱类化合物,其新颖复杂的化学结构、广泛而显著的生物活性、全新独特的作用机制、奇缺的自然资源使其受到了植物学家、化学家、药理学家、分子生物学家的极大青睐,使其成为20世纪下半叶举世瞩目的抗癌明星和研究重点,包括寻找新的生物资源、化学全合成、半合成、衍生物制备、生物转化、生物合成、生物工程、构-效关系研究、作用机制研究、药理学和药效学等研究。2011年是发现紫杉醇结构40周年,对紫杉醇发现的曲折历史过程进行回顾和总结,以纪念这一伟大发现并纪念为紫杉醇的研究与第二代紫杉醇的开发作出贡献的科学家。     

Drug-like properties: guiding principles for the design of natural product libraries

While natural products or their derivatives and mimics have contributed around 50% of current drugs, there has been no approach allowing front-loading of chemical space compliant with lead- and drug-like properties. The importance of physicochemical properties of molecules in the development of orally bioavailable drugs has been recognized. Classical natural product drug discovery has only been able to undertake this analysis retrospectively after compounds are isolated and structures elucidated. The present approach addresses front-loading of both extracts and subsequent fractions with desired physicochemical properties prior to screening for drug discovery. The physicochemical profiles of natural products active against two neglected disease targets, malaria and African trypanosomiasis, are presented based on this strategy. This approach can ensure timely development of natural product leads at a hitherto unachievable rate.     

内生菌与天然药物

随着对植物内生菌的研究日益深入，内生菌次生代谢产物的研究趋向活跃。研究表明，内生菌具有丰富的次生代谢产物多样性。众多内生菌活性成分己得到了分离纯化和鉴定，成为发现新型化合物的一个重要来源和途径。本文就近年来内生菌在天然药物研究方面取得的进展进行简要综述。     

Challenges and rewards of research in marine natural products chemistry in Brazil

Brazil is blessed with a great biodiversity, which constitutes one of the most important sources of biologically active compounds, even if it has been largely underexplored. As is the case of the Amazon and Atlantic rainforests, the Brazilian marine fauna remains practically unexplored in the search for new biologically active natural products. Considering that marine organisms have been shown to be one of the most promising sources of new bioactive compounds for the treatment of different human diseases, the 8000 km of the Brazilian coastline represents a great potential for finding new pharmacologically active secondary metabolites. This review presents the status of marine natural products chemistry in Brazil, including results reported by different research groups with emphasis on the isolation, structure elucidation, and evaluation of biological activities of natural products isolated from sponges, ascidians, octocorals, and Opistobranch mollusks. A brief overview of the first Brazilian program on the isolation of marine bacteria and fungi, directed toward the production of biologically active compounds, is also discussed. The current multidisciplinary collaborative program under development at the Universidade de S?o Paulo proposes to establish a new paradigm toward the management of the Brazilian marine biodiversity, integrating research on the species diversity, ecology, taxonomy, and biogeography of marine invertebrates and microorganisms. This program also includes a broad screening program of Brazilian marine bioresources, to search for active compounds that may be of interest for the development of new drug leads.     

海洋天然产物研究概述

近年来海洋天然产物越来越引起科学家们的注意,在浩瀚的海洋中存在着大量令人激动、活性独特、结构新颖的次生代谢产物。海洋天然产物已成为发现重要先导药物和新的生物作用机制的主要源泉。对目前海洋天然产物研究概况进行综述,其中重点介绍大环内酯类和聚醚类等化合物。     

Research progress of Chinese herbal medicine compounds and their bioactivities: Fruitful 2020

Traditional Chinese medicines (TCMs) have continued to be a treasure trove. The study of chemodiversity and versatility of bioactivities has always been an important content of pharmacophylogeny. There is amazing progress in the discovery and research of natural components with novel structures and significant bioactivities in 2020. In this paper we review 271 valuable natural products, including terpenoids, steroids, flavonoids, phenylpropanoids, phenolics, nitrogen containing compounds and essential oil, etc., isolated and identified from TCMs published in journals of Chinese Traditional and Herbal Drugs (Zhong Cao Yao) and Chinese Herbal Medicines (CHMs), and focus on their structures, source organisms, and relevant bioactivities, paying special attention to structural characteristics of novel compounds and newly revealed pharmacological properties of known compounds. It is worth noting that natural products with antitumor activity still constitute the primary object of research. Among the reported compounds, two new triterpenoids, i.e., ursolic acid 3-O-β-cis-caffeate and mollugoside E, display remarkable cytotoxicity against PC-9 and HL-60 cell lines, respectively. Three known phenolic compounds, i.e., pyoluteorin, 4-hydroxy-3-methoxy cinnamaldehyde and 3,7-dimethoxy-5-hydroxy-1,4-phenanthrenequinone, exhibit significant cytotoxicity against multiple cell lines. Numerous studies on the free radical scavenging activity of reported compounds are currently underway. In vitro, three known phenolic compounds, i.e., 3,4-O-dicaffeoylquinic acid methyl ester, 3,4,5-O-tricaffeoylquinic acid methyl ester and arbutin, had more considerable antioxidant activities than vitamin C. The anti-inflammatory, anti-diabetic, hypolipidemic, neuroprotective and antimicrobial activities of isolated compounds are also encouraging. The structural characteristics and bioactivities of TCM compounds highlighted here reflect the enormous progress of CHM research in 2020 and will play a positive role in the future drug discovery and development. According to pharmacophylogeny, the phylogenetic distribution of compounds with different natures and flavors can be explored, with view to better mining TCM resources.     

Medicinal bulbous plants of South Africa and their traditional relevance in the control of infectious diseases

Natural products are becoming more important in modern-day society as man is moving away from synthetic products, which can be detrimental to the environment and human health. Scientific research on the healing properties and bioactivity of natural compounds, especially of plant origin, has been extensive particularly in the Western world. However, a rich heritage of floral biodiversity is found in developing countries. South Africa, a country with a strong history of traditional healing, hosts a variety of around 30000 plant species. Indigenous bulbous plants of importance to South African traditional healers mainly belong to the Amaryllidaceae and Hyacinthaceae families. A number of these plants have particular uses as disinfectants and anti-inflammatory agents, although there is still a lack of scientific research regarding their unique pharmacological compounds.