Natural product



 It has been suggested that secondary metabolite be merged into this article or section. (Discuss)
 

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 design.

A natural product can be considered as such even if it can be prepared by total synthesis.

Not all natural products can be fully paclitaxel . Such compounds can only be harvested from their natural source - a process which can be tedious, time consuming, and expensive, as well as being potentially unsustainable for the resource. 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.[1]

Semisynthetic procedures can sometimes get round 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 paclitaxel which was manufactured by extracting 10-deacetylbaccatin III from the needles of the yew, then carrying out a four-stage synthesis.

Natural sources

Natural products may be extracted from tissues of terrestrial plants, marine organisms or 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.

Screening of natural products

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 analogues.

The plant kingdom

Plants have always been a rich source of lead compounds (e.g. 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.

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 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 ciclosporin which is used to suppress the immune response after transplantation operations.

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 bryostatins, dolostatins, and cephalostatins.

Animal sources

Animals can sometimes be a source of new lead compounds. For example, a series of epibatidine was obtained from the skin extracts of the Ecuadorian poison frog.

Venoms and toxins

Venoms and toxins from animals, plants, snakes, spiders, scorpions, insects, and 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 captopril.

The anticholinergic drugs.

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, dantron.

The extensive records of quinine).

It can be challenging to obtain information from practitioners of traditional medicine unless a genuine long term relationship is made. Ethnobotanist Richard Schultes had the good sense to approach the Amazonian shamans with respect, dealing with them on their terms and not as a latter-day conquistador. He became a "depswa" - medicine man - sharing their rituals while gaining knowledge. They responded to his inquiries in kind, leading to countless new medicines for treating our "civilized" illnesses.[3] On the other hand Cherokee herbalist David Winston recounts how his uncle, a medicine priest, would habitually give misinformation to 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.[4] The issue of rights to medicine derived from native plants used and frequently cultivated by native healers complicates the issue.

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 very much on the structure, stability, and quantity of the compound. For example, chromatography that the successful isolation and purification of penicillin and other natural products became feasible.

See also

References

  1. ^ 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
  2. ^ Dan Bensky, Steven Clavey, Erich Stoger, and Andrew Gamble Chinese Herbal Medicine: Materia Medica, Third Edition 2004
  3. ^ Wade Davis One River 1997
  4. ^ Hernan Garcia, Antonio Sierra, Hilberto Balam, and Jeff Connant Wind in the Blood: Mayan Healing & Chinese Medicine. 1999

Further reading

  • James Ralph Hanson, Natural Products: The Secondary Metabolites (2003), Royal Society of Chemistry, ISBN 0854044906
  • Xiao-Tian Liang, Wei-Shuo Fang (editors), Medicinal Chemistry of Bioactive Natural Products (2006), Wiley-Interscience, ISBN 0471739332
  • Peter B. Kaufman, Natural products from plants (1999), CRC Press, ISBN 084933134X
  • Meenakshi. Sivakumar, S. Meenakshi, Sujata V. Bhat, Bhimsen A. Nagasampagi, Chemistry of Natural Products (2005), Springer, ISBN 3540406697
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Natural_product". A list of authors is available in Wikipedia.