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Natural Products

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Paclitaxel (Taxol) is a natural product derived from the Yew tree.[1]
A natural product is a chemical compound or substance produced by a living organism - found in nature that usually has a pharmacological or biological activity for use in pharmaceutical drug discovery and drug design. A natural product can be considered as such even if it can be prepared by total synthesis.
These small molecules provide the source or inspiration for the majority of FDA-approved agents and continue to be one of the major sources of inspiration for drug discovery. In particular, these compounds are important in the treatment of life-threatening conditions.[2] Contents[hide] * 1 Natural sources * 2 Screening of natural products * 2.1 The plant kingdom * 2.2 The microbial world * 2.3 The marine world * 2.4 Animal sources * 2.5 Venoms and toxins * 3 Traditional Medicine * 4 Isolation and purification * 5 Synthesis * 6 See also * 7 References * 8 External links * 9 Further reading |
[edit] Natural sources
Natural products may be extracted from tissues of terrestrial plants, marine organisms or microorganism fermentation broths. A crude (untreated) extract from any one of these sources typically contains novel, structurally diverse chemical compounds, which the natural environment is a rich source of.
Chemical diversity in nature is based on biological and geographical diversity, so researchers travel around the world obtaining samples to analyze and evaluate in drug discovery screens or bioassays. This effort to search for natural products is known as bioprospecting.
[edit] Screening of natural products
Pharmacognosy provides the tools to identify, select and process natural products destined for medicinal use. Usually, the natural product compound has some form of biological activity and that compound is known as the active principle - such a structure can act as a lead compound (not to be confused with compounds containing the element lead). Many of today's medicines are obtained directly from a natural source.
On the other hand, some medicines are developed from a lead compound originally obtained from a natural source. This means the lead compound: * can be produced by total synthesis, or * can be a starting point (precursor) for a semisynthetic compound, or * can act as a template for a structurally different total synthetic compound.
This is because most biologically active natural product compounds are secondary metabolites with very complex structures. This has an advantage in that they are extremely novel compounds but this complexity also makes many lead compounds' synthesis difficult and the compound usually has to be extracted from its natural source - a slow, expensive and inefficient process. As a result, there is usually an advantage in designing simpler analogues.
[edit] The plant kingdom
Plants have always been a rich source of lead compounds (e.g. Alkaloids, morphine, cocaine, digitalis, quinine, tubocurarine, nicotine, and muscarine). Many of these lead compounds are useful drugs in themselves (e.g. Alkaloids, morphine and quinine), and others have been the basis for synthetic drugs (e.g. local anaesthetics developed from cocaine). Clinically useful drugs which have been recently isolated from plants include the anticancer agent paclitaxel (Taxol) from the yew tree, and the antimalarial agent artemisinin from Artemisia annua.
Plants provide a large bank of rich, complex and highly varied structures which are unlikely to be synthesized in laboratories. Furthermore, evolution has already carried out a screening process itself whereby plants are more likely to survive if they contain potent compounds which deter animals or insects from eating them. Even today, the number of plants that have been extensively studied is relatively very few and the vast majority have not been studied at all.
[edit] The microbial world
Microorganisms such as bacteria and fungi have been invaluable for discovering drugs and lead compounds. These microorganisms produce a large variety of antimicrobial agents which have evolved to give their hosts an advantage over their competitors in the microbiological world.
The screening of microorganisms became highly popular after the discovery of penicillin. Soil and water samples were collected from all over the world in order to study new bacterial or fungal strains, leading to an impressive arsenal of antibacterial agents such as the cephalosporins, tetracyclines, aminoglycosides, rifamycins, and chloramphenicol.
Although most of the drugs derived from microorganisms are used in antibacterial therapy, some microbial metabolites have provided lead compounds in other fields of medicine. For example, asperlicin - isolated from Aspergillus alliaceus - is a novel antagonist of a peptide hormone called cholecystokinin (CCK) which is involved in the control of appetite. CCK also acts as a neurotransmitter in the brain and is thought to be involved in panic attacks. Analogues of asperlicin may therefore have potential in treating anxiety. Other examples include the fungal metabolite lovastatin, which was the lead compound for a series of drugs that lower cholesterol levels, and another fungal metabolite called ciclosporin which is used to suppress the immune response after transplantation operations.
[edit] The marine world
In recent years, there has been a great interest in finding lead compounds from marine sources. Coral, sponges, fish, and marine microorganisms have a wealth of biologically potent chemicals with interesting inflammatory, antiviral, and anticancer activity. For example, curacin A is obtained from a marine cyanobacterium and shows potent antitumor activity. Other antitumor agents derived from marine sources include eleutherobin, discodermolide, bryostatins, dolostatins, and cephalostatins.
[edit] Animal sources
Animals can sometimes be a source of new lead compounds. For example, a series of antibiotic peptides were extracted from the skin of the African clawed frog and a potent analgesic compound called epibatidine was obtained from the skin extracts of the Ecuadorian poison frog.
[edit] Venoms and toxins
Venoms and toxins from animals, plants, snakes, spiders, scorpions, insects, and microorganisms are extremely potent because they often have very specific interactions with a macromolecular target in the body. As a result, they have proved important tools in studying receptors, ion channels, and enzymes. Many of these toxins are polypeptides (e.g. α-bungarotoxin from cobras). However, non-peptide toxins such as tetrodotoxin from the puffer fish are also extremely potent.
Venoms and toxins have been used as lead compounds in the development of novel drugs. For example, teprotide, a peptide isolated from the venom of the Brazilian viper, was the lead compound for the development of the antihypertensive agents cilazapril and captopril.
The neurotoxins from Clostridium botulinum are responsible for serious food poisoning (botulism), but they have a clinical use as well. They can be injected into specific muscles (such as those controlling the eyelid) to prevent muscle spasm. These toxins prevent cholinergic transmission and could well prove a lead for the development of novel anticholinergic drugs.
[edit] Traditional Medicine
In the past, traditional peoples or ancient civilizations depended greatly on local flora and fauna for their survival. They would experiment with various berries, leaves, roots, animal parts or minerals to find out what effects they had. As a result, many crude drugs were observed by the local healer or shaman to have some medical use. Although some preparations may have been dangerous, or worked by a ceremonial or placebo effect, traditional healing systems usually had a substantial active pharmacopoeia, and in fact most western medicines up until the 1920s were developed this way. Some systems, like traditional Chinese medicine or Ayurveda were fully as sophisticated and as documented systems as western medicine, although they might use different paradigms. Many of these aqueous, ethanolic, distilled, condensed or dried extracts do indeed have a real and beneficial effect, and a study of ethnobotany can give clues as to which plants might be worth studying in more detail. Rhubarb root has been used as a purgative for many centuries. In China, it was called "The General" because of its "galloping charge" and was only used for one or two doses unless processed to reduce its purgative qualities. (Bulk laxatives would follow or be used on weaker patients according to the complex laxative protocols of the medical system.[3]) The most significant chemicals in rhubarb root are anthraquinones, which were used as the lead compounds in the design of the laxative dantron.
The extensive records of Chinese medicine about response to Artemisia preparations for malaria also provided the clue to the novel antimalarial drug artemisinin. The therapeutic properties of the opium poppy (active principle morphine) were known in Ancient Egypt, were those of the Solanaceae plants in ancient Greece (active principles atropine and hyoscine). The snakeroot plant was well regarded in India (active principle reserpine), and herbalists in medieval England used extracts from the willow tree(salicin) and foxglove (active principle digitalis - a mixture of compounds such as digitoxin, digitonin, digitalin). The Aztec and Mayan cultures of Mesoamerica used extracts from a variety of bushes and trees including the ipecacuanha root (active principle emetine), coca bush (active principle cocaine), and cinchona bark (active principle quinine).
It can be challenging to obtain information from practitioners of traditional medicine unless a genuine long term relationship is made. Ethnobotanist Richard Schultes approached the Amazonian shamans with respect, dealing with them on their terms. He became a "depswa" - medicine man - sharing their rituals while gaining knowledge. They responded to his inquiries in kind, leading to new medicines.[4] On the other hand Cherokee herbalist David Winston recounts how his uncle, a medicine priest, would habitually give misinformation to the visiting ethnobotanists. The acupuncturists who investigated Mayan medicine recounted in Wind in the Blood had something to share with the native healers and thus were able to find information not available to anthropologists.[5] The issue of rights to medicine derived from native plants used and frequently cultivated by native healers complicates this issue.
[edit] Isolation and purification
If the lead compound (or active principle) is present in a mixture of other compounds from a natural source, it has to be isolated and purified. The ease with which the active principle can be isolated and purified depends much on the structure, stability, and quantity of the compound. For example, Alexander Fleming recognized the antibiotic qualities of penicillin and its remarkable non-toxic nature to humans, but he disregarded it as a clinically useful drug because he was unable to purify it. He could isolate it in aqueous solution, but whenever he tried to remove the water, the drug was destroyed. It was not until the development of new experimental procedures such as freeze drying and chromatography that the successful isolation and purification of penicillin and other natural products became feasible.
[edit] Synthesis
Not all natural products can be fully synthesized and many natural products have very complex structures that are too difficult and expensive to synthesize on an industrial scale. These include drugs such as penicillin, morphine, and paclitaxel (Taxol). Such compounds can only be harvested from their natural source - a process which can be tedious, time consuming, and expensive, as well as being wasteful on the natural resource. For example, one yew tree would have to be cut down to extract enough paclitaxel from its bark for a single dose.[6] Furthermore, the number of structural analogues that can be obtained from harvesting is severely limited.
A further problem is that isolates often work differently than the original natural products which have synergies and may combine, say, antimicrobial compounds with compounds that stimulate various pathways of the immune system:
Many higher plants contain novel metabolites with antimicrobial and antiviral properties. However, in the developed world almost all clinically used chemotherapeutics have been produced by in vitro chemical synthesis. Exceptions, like taxol and vincristine, were structurally complex metabolites that were difficult to synthesize in vitro. Many non-natural, synthetic drugs cause severe side effects that were not acceptable except as treatments of last resort for terminal diseases such as cancer. The metabolites discovered in medicinal plants may avoid the side effect of synthetic drugs, because they must accumulate within living cells.[7]
Semisynthetic procedures can sometimes get around these problems. This often involves harvesting a biosynthetic intermediate from the natural source, rather than the final (lead) compound itself. The intermediate could then be converted to the final product by conventional synthesis. This approach can have two advantages. First, the intermediate may be more easily extracted in higher yield than the final product itself. Second, it may allow the possibility of synthesizing analogues of the final product. The semisynthetic penicillins are an illustration of this approach. Another recent example is that of paclitaxel. It is manufactured by extracting 10-deacetylbaccatin III from the needles of the yew tree, then carrying out a four-stage synthesis.
[edit] See also * Ayurveda * Chinese medicine * Ethnobotany * Journal of Natural Products * Pharmacognosy * Phytotherapy * Secondary metabolite
[edit] References 1. ^ Cutler, Stephen J.; Cutler, Horace G. (2000). Biologically active natural products: pharmaceuticals. CRC Press. p. 5. ISBN 9780849318870. http://books.google.com/?id=fOfFNOMkks8C&pg=PA5&dq=Paclitaxel+natural+product&cd=9#v=onepage&q=Paclitaxel%20natural%20product. 2. ^ Newman DJ, Cragg GM Natural products as sources of new drugs over the last 25 years. Journal of Natural Products 70, 461-477 (2007). 3. ^ Dan Bensky, Steven Clavey, Erich Stoger, and Andrew Gamble Chinese Herbal Medicine: Materia Medica, Third Edition 2004 4. ^ Wade Davis One River 1997 5. ^ Hernan Garcia, Antonio Sierra, Hilberto Balam, and Jeff Connant Wind in the Blood: Mayan Healing & Chinese Medicine. 1999 6. ^ "The American Society of Pharmacognosy - Story of Taxol". http://www.phcog.org/Taxus/Taxus_Web.html. 7. ^ El-Shemy HA, Aboul-Enein AM, Aboul-Enein KM, Fujita K Willow Leaves’ Extracts Contain Anti-Tumor Agents Effective against Three Cell Types.: PLoS ONE. 2007;2:e178
[edit] External links * Natural Products Chemistry (Michigan State University, Department of Chemistry) * Natural Product Reports (Royal Society of Chemistry) * Journal of Natural Products (American Chemical Society) * Natural Products 13C NMR Database (A tool for rapid identification of natural products) * Synthetic resources are man-made, made by using natural resources, or they are modified to be suitable for use. Natural resources are combined to make an un-natural resouce (i.e. synthetic). Basic examples of these resources are: * Cardboard, wire, paper etc. * Natural resources are not modified, and they can be used as 'nature' has made them. Examples of these resources are: * Fruits, vegetables, wheat, timber etc. *
Read more: http://wiki.answers.com/Q/What_is_the_difference_between_synthetic_and_natural_resourc

es#ixzz1JEYxF8Hd * Not all vitamins were created equal – or natural. To be more specific, over 90% of the vitamins purchased by consumers, whether in a supermarket, pharmacy or health food store, are substances formulated in a laboratory. These synthetic, fractionated vitamins simply cannot be easily absorbed by the body which means that when you take them you are literally flushing money down the toilet. * How do you know if you are ingesting a synthetic vitamin or one made from all natural fruits and vegetables? It’s easy really, just read the label. If your vitamin’s ingredients sound like something from a chemistry lab then that’s exactly what they are; chemically created synthetic vitamins. * For example, here is a list of the major ingredients of a leading vitamin brand found in just about every grocery store and pharmacy in America and taken by millions of unsuspecting consumers every day: magnesium oxide; dicalcium phosphate; ascorbic acid; di-alpha tocopheryl acetate; ferrous fumarate; croscarmellose sodium; potassium chloride; calcium panthenate; pyridoxine hydrochloride; hypromelose; polyethelene glycol; manganese sulfate; pytonadione and cyanocobalamin (a synthetic form of vitamin B-12). Do you have any idea what any of those things are? You’d have to be a chemist to know what you are putting in your system with a list like that. * Now look at the list of ingredients on a box of 9 a Day Plus where the vitamins come from these natural sources: carrots; acerola cherry; soy; sunflower; corn; spinach; blueberry; raspberry; apple; cranberry; grape; aloe vera; beets; etc. It is easy to see that there is a difference so now you need to understand why that difference really matters to your health. * The truth is that even though they are often called natural, most non-food vitamins are isolated chemical substances which are crystalline in structure. And most vitamins in these supplements are made or processed with petroleum derivatives or hydrogenated sugars. Vitamins naturally found in food are not crystalline and never isolated. Vitamins found in any real foodare chemically and structurally different from those commonly found in “natural vitamin” formulas. Since they are different, you should consider non-food vitamins as vitamin “analogues” or imitations and not actually vitamins. * The body treats these isolated – or fractionated – vitamins as they would any foreign or chemical substance: it rejects them. This is why the bulk of the content simply passes through the body and is never assimilated into your system. This is why over-consumption of these kinds of vitamins can actually be detrimental to your health as they can build up in the liver or kidneys and do more harm than good. * You may be thinking that your vitamins are different because you buy them at a health food store. You are probably wrong. Here is a list of ingredients from a bottle of vitamin C from a major brand found in a local health food store: ascorbic acid; cellulose gel; corn starch; hydropxypropyl cellulose; hydroxypropyl methylcellulose; magnesium state; silicon dioxide; stearic acid;polyethylene glycol. The front of the label says all natural and it’s on a shelf in a reputable health food store, but the ingredients label doesn’t lie – there’s nothing natural about this product at all. * You may have noticed that a common ingredient is ascorbic acid. Some of you may be thinking that ascorbic acid is in fact vitamin C but here is another myth about the vitamins we waste money on. Though the FDA allows Ascorbic Acid to be labeled as vitamin C, it really is NOT vitamin C. It is only part of the vitamin C complex and what is known as a fractionated vitamin. This is true for many of the vitamins you may be taking now. Instead of getting the entire benefit of the vitamin you are buying you are probably getting only part of the vitamin, which is like taking no vitamin at all. The body cannot use a vitamin unless it is in its entirety. It doesn’t use the isolated parts properly so you might as well not bother taking it at all. * 9 a Day Plus uses complete, natural vitamins from fruits and vegetables that your body can easily absorb and put to use. Feel the 9 a Day difference and get all the nutritional benefits from your supplements that you pay for.

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Retail Advertising and Marketing

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Clean Edge Razor

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