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Natural Products: Drug Discovery and Therapeutic Medicine

Lixin Zhang ; Arnold L. Demain (eds.)

Resumen/Descripción – provisto por la editorial

No disponible.

Palabras clave – provistas por la editorial

Pharmacy

Disponibilidad
Institución detectada Año de publicación Navegá Descargá Solicitá
No detectada 2005 SpringerLink

Información

Tipo de recurso:

libros

ISBN impreso

978-1-58829-383-1

ISBN electrónico

978-1-59259-976-9

Editor responsable

Springer Nature

País de edición

Reino Unido

Fecha de publicación

Información sobre derechos de publicación

© Humana Press Inc. 2005

Cobertura temática

Tabla de contenidos

Arsenic Trioxide and Leukemia

Guo-Qiang Chen; Qiong Wang; Hua Yan; Zhu Chen

Cumulative evidence indicates that traditional Chinese medicine (TCM) is an important resource for discoveries of drugs against cancer. Arsenic, a common, naturally existing substance, is rarely found in its pure elemental state in nature. In addition to the organic arsenicals, there are three major inorganic arsenic forms: red arsenic (AsS), yellow arsenic (AsS), and white arsenic (AsO, ATO). Based on the basic TCM theory of “using poison against poison,” a group from Harbin Medical University in the northeastern region of China in the early 1970s introduced intravenous infusion of “Ailing-1 (anticancer-1),” a solution of crude ATO and herbal extracts, into cancer therapy. After a lengthy study in more than 1000 patients with various kinds of cancers, acute promyelocytic leukemia (APL), a specific subtype of acute myeloid leukemia characterized by the failure of differentiation/ maturation towards granulocytic cells at the promyelocytic stage, was determined to be an excellent target for “Ailing-1” therapy. At the same time, there were reports of using the formula called “niu huang jie du pian” (containing xiong huang) or just using xiong huang (realgar) by itself to treat APL. A formula of Qing Dai (indigo) containing xiong huang as the main Chinese herb was reported to result in 98.3% total remission.

Part III - Specific Groups of Drugs | Pp. 251-272

New Methods to Access Microbial Diversity for Small Molecule Discovery

Karsten Zengler; Ashish Paradkar; Martin Keller

Natural-product-derived drugs are a major portion of the total number of approved drugs in the antibacterial area. The majority of bacteria and fungi in the environment is only known by molecular fingerprints and has resisted cultivation. Therefore, new methods have been developed to access this tremendous microbial diversity for the discovery of novel small molecules. These culture-dependent and -independent methods include a novel high-throughput cultivation technology as well as a recombinant approach to discover and express novel natural products.

Part IV - Microbial Diversity | Pp. 275-293

Accessing the Genomes of Uncultivated Microbes for Novel Natural Products

Asuncion Martinez; Joern Hopke; Ian A. MacNeil; Marcia S. Osburne

Recent findings suggest that only 1% or less of the total number of soil microbial species can be easily cultivated. The fact that uncultured species represent spectacular microbial diversity has sparked great interest in these microorganisms as a potentially prolific source of untapped genetic diversity encoding novel natural products. Multiple approaches are being developed to access this diversity, such as methods to improve the ability to cultivate some of these organisms, most of which are not easily grown under standard laboratory conditions. Here we discuss an alternative approach, aimed at developing technologies for gaining access to the genomes of uncultivated microbes by creating environmental DNA libraries. This method involves isolating large DNA fragments (100–300 kb) from soil microorganisms (or from microorganisms derived from other environments), and inserting these fragments into a bacterial vector, thus generating recombinant DNA libraries. Such libraries are then used to identify novel natural products by various means, including expression of the DNA in a heterologous host strain and screening for activities, or by directly analyzing the DNA for genes of interest. The recombinant approach thus obviates the need for culturing diverse microorganisms and provides a relatively unbiased sampling of the vast untapped genetic diversity present in various microenvironments. As an additional advantage, the genes encoding a product of interest are already isolated and can be analyzed using the tools of bioinformatics, thus providing a potential boost to the efforts of analytical chemists to identify the product. Furthermore, the possibility of regulating the expression of isolated environmental gene clusters or combining them with genes for other pathways to obtain new compounds could furnish a further advantage over traditional naturalproduct discovery methodologies.

Part IV - Microbial Diversity | Pp. 295-312

New Natural-Product Diversity From Marine Actinomycetes

Paul R. Jensen; William Fenical

There is currently renewed interest in the study of microorganisms as a source of structurally unique and pharmacologically active natural products. Actinomycetes, being the single most productive source of naturally occurring antibiotics, are a logical component of these studies, and success with this group will be enhanced by the inclusion of previously unknown taxa. Recent studies of marine-derived actinomycetes have revealed the widespread distribution of unique marine taxa residing in ocean sediments. Chemical studies of these strains, focusing on members of the new genus , have led to a high rate of novel secondary metabolite discovery, including molecules with potent biological activity. Given the encouraging results from preliminary studies of these newly described marine bacteria, it seems clear that marine actinomycetes represent an important future resource for small-molecule drug discovery.

Part V - Specific Sources | Pp. 315-328

Novel Natural Products From Rainforest Endophytes

Gary Strobel; Bryn Daisy; Uvidelio Castillo

Endophytic microorganisms are found in virtually every higher plant on earth. These organisms reside in the living tissues of the host plant and do so in a variety of relationships, ranging from symbiotic to pathogenic. Endophytes may contribute to their host plant by producing a plethora of substances that provide protection and survival value to the plant. Ultimately, these compounds, once isolated and characterized, may also have potential for use in modern medicine. Novel antibiotics, antimycotics, immunosuppressants, and anticancer compounds are only a few examples of what has been found after the isolation and culturing of individual endophytes followed by purification and characterization of some of their natural products. The potential of finding new drugs that may be effective candidates for treating newly developing diseases in humans is great.

Part V - Specific Sources | Pp. 329-351

Biological, Economic, Ecological, and Legal Aspects of Harvesting Traditional Medicine in Ecuador

Alexandra Guevara-Aguirre; Ximena Chiriboga

Harvesting and further developing the traditional herbal remedies in Ecuador (THME) is a very promising area from various perspectives that might be considered and subject to serious analysis. The coincidence of the richest biodiversity in South America confined within a small geographical area presents inherent scientific, pragmatic, and logistical advantages; moreover, Ecuador at this time uses the US dollar as its only currency. This implies that any economic planning can be done by investors using the widest known monetary instrument. Another important development taking place in this country is the effort presently under way to implement proper legal measures to protect foreign investment. At any rate, the endeavor of harvesting and developing THM requires in Ecuador, as in any other fragile location, an integral approach to avoid serious mistakes seen in the past. If such conditions are met, it is very likely that the participating individuals will be conscientious enough to place the interests of collectivity ahead of their own and protect, as their own, the very source that generates any potential earnings: a healthy and rationally used environment.

Part V - Specific Sources | Pp. 353-370