Natural product

Natural product

Overview
A natural product is a chemical compound
Chemical compound
A chemical compound is a pure chemical substance consisting of two or more different chemical elements that can be separated into simpler substances by chemical reactions. Chemical compounds have a unique and defined chemical structure; they consist of a fixed ratio of atoms that are held together...

 or substance produced by a living organism - found in nature that usually has a pharmacological or biological activity for use in pharmaceutical drug discovery
Drug discovery
In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are discovered or designed.In the past most drugs have been discovered either by identifying the active ingredient from traditional remedies or by serendipitous discovery...

 and drug design
Drug design
Drug design, also sometimes referred to as rational drug design or structure-based drug design, is the inventive process of finding new medications based on the knowledge of the biological target...

. A natural product can be considered as such even if it can be prepared by total synthesis
Total synthesis
In organic chemistry, a total synthesis is, in principle, the complete chemical synthesis of complex organic molecules from simpler pieces, usually without the aid of biological processes. In practice, these simpler pieces are commercially available in bulk and semi-bulk quantities, and are often...

.

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.
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Encyclopedia
A natural product is a chemical compound
Chemical compound
A chemical compound is a pure chemical substance consisting of two or more different chemical elements that can be separated into simpler substances by chemical reactions. Chemical compounds have a unique and defined chemical structure; they consist of a fixed ratio of atoms that are held together...

 or substance produced by a living organism - found in nature that usually has a pharmacological or biological activity for use in pharmaceutical drug discovery
Drug discovery
In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are discovered or designed.In the past most drugs have been discovered either by identifying the active ingredient from traditional remedies or by serendipitous discovery...

 and drug design
Drug design
Drug design, also sometimes referred to as rational drug design or structure-based drug design, is the inventive process of finding new medications based on the knowledge of the biological target...

. A natural product can be considered as such even if it can be prepared by total synthesis
Total synthesis
In organic chemistry, a total synthesis is, in principle, the complete chemical synthesis of complex organic molecules from simpler pieces, usually without the aid of biological processes. In practice, these simpler pieces are commercially available in bulk and semi-bulk quantities, and are often...

.

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.

Natural sources


Natural products may be extracted from tissue
Tissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...

s of terrestrial plants, marine
Marine (ocean)
Marine is an umbrella term. As an adjective it is usually applicable to things relating to the sea or ocean, such as marine biology, marine ecology and marine geology...

 organisms or microorganism
Microorganism
A microorganism or microbe is a microscopic organism that comprises either a single cell , cell clusters, or no cell at all...

 fermentation
Fermentation (biochemistry)
Fermentation is the process of extracting energy from the oxidation of organic compounds, such as carbohydrates, using an endogenous electron acceptor, which is usually an organic compound. In contrast, respiration is where electrons are donated to an exogenous electron acceptor, such as oxygen,...

 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


Pharmacognosy
Pharmacognosy
Pharmacognosy is the study of medicines derived from natural sources. The American Society of Pharmacognosy defines pharmacognosy as "the study of the physical, chemical, biochemical and biological properties of drugs, drug substances or potential drugs or drug substances of natural origin as well...

 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
Lead compound
A lead compound in drug discovery is a chemical compound that has pharmacological or biological activity and whose chemical structure is used as a starting point for chemical modifications in order to improve potency, selectivity, or pharmacokinetic parameters.Lead compounds are often found in...

 (not to be confused with compounds containing the element lead
Lead
Lead is a main-group element in the carbon group with the symbol Pb and atomic number 82. Lead is a soft, malleable poor metal. It is also counted as one of the heavy metals. Metallic lead has a bluish-white color after being freshly cut, but it soon tarnishes to a dull grayish color when exposed...

). Many of today's medicines are obtained directly from a natural source.

On the other hand, some medicines are developed from a lead compound
Lead compound
A lead compound in drug discovery is a chemical compound that has pharmacological or biological activity and whose chemical structure is used as a starting point for chemical modifications in order to improve potency, selectivity, or pharmacokinetic parameters.Lead compounds are often found in...

 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 analogue
Analog (chemistry)
In chemistry, a structural analog , also known as chemical analog or simply analog, is a compound having a structure similar to that of another one, but differing from it in respect of a certain component. It can differ in one or more atoms, functional groups, or substructures, which are replaced...

s.

The plant kingdom


Plants have always been a rich source of lead compounds (e.g. Alkaloids, morphine
Morphine
Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...

, cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...

, digitalis
Digitalis
Digitalis is a genus of about 20 species of herbaceous perennials, shrubs, and biennials that are commonly called foxgloves. This genus was traditionally placed in the figwort family Scrophulariaceae, but recent reviews of phylogenetic research have placed it in the much enlarged family...

, quinine
Quinine
Quinine is a natural white crystalline alkaloid having antipyretic , antimalarial, analgesic , anti-inflammatory properties and a bitter taste. It is a stereoisomer of quinidine which, unlike quinine, is an anti-arrhythmic...

, tubocurarine
Tubocurarine
Tubocurarine is a neuromuscular-blocking drug or skeletal muscle relaxant in the category of non-depolarizing neuromuscular-blocking drugs, used adjunctively in anesthesia to provide skeletal muscle relaxation during surgery or mechanical ventilation...

, nicotine
Nicotine
Nicotine is an alkaloid found in the nightshade family of plants that constitutes approximately 0.6–3.0% of the dry weight of tobacco, with biosynthesis taking place in the roots and accumulation occurring in the leaves...

, and muscarine
Muscarine
Muscarine, L--muscarine, or muscarin is a natural product found in certain mushrooms, particularly in Inocybe and Clitocybe species, such as the deadly C. dealbata. Mushrooms in the genera Entoloma and Mycena have also been found to contain levels of muscarine which can be dangerous if ingested...

). 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
Paclitaxel
Paclitaxel is a mitotic inhibitor used in cancer chemotherapy. It was discovered in a U.S. National Cancer Institute program at the Research Triangle Institute in 1967 when Monroe E. Wall and Mansukh C. Wani isolated it from the bark of the Pacific yew tree, Taxus brevifolia and named it taxol...

 (Taxol) from the yew tree, and the antimalarial agent artemisinin
Artemisinin
Artemisinin , also known as Qinghaosu , and its derivatives are a group of drugs that possess the most rapid action of all current drugs against falciparum malaria. Treatments containing an artemisinin derivative are now standard treatment worldwide for falciparum malaria...

 from Artemisia annua
Artemisia annua
Artemisia annua, also known as Sweet Wormwood, Sweet Annie, Sweet Sagewort or Annual Wormwood , is a common type of wormwood that is native to temperate Asia, but naturalized throughout the world.-Characteristics:...

.

Plants provide a large bank of rich, complex and highly varied structures which are unlikely to be synthesized in laboratories. Furthermore, evolution
Evolution
Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...

 has already carried out a screening process itself whereby plants are more likely to survive if they contain potent
Potency
Potency may refer to:* Potency , a measure of the activity of a drug in a biological system* Virility* Potency is a measure of the differentiation potential of stem cells...

 compounds which deter animals 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.

Major classes of molecules include phytosterol
Phytosterol
Phytosterols, which encompass plant sterols and stanols, are steroid compounds similar to cholesterol which occur in plants and vary only in carbon side chains and/or presence or absence of a double bond. Stanols are saturated sterols, having no double bonds in the sterol ring structure. More than...

s, alkaloid
Alkaloid
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...

s, natural phenol
Natural phenol
Natural phenols, bioavailable phenols, plant phenolics, low molecular weight phenols or phenoloids are a class of natural products. They are small molecules containing one or more phenolic group. These molecules are smaller in size than polyphenols, containing less than 12 phenolic groups...

s and polyphenol
Polyphenol
Polyphenols are a structural class of natural, synthetic, and semisynthetic organic chemicals characterized by the presence of large multiples of phenol structural units...

s.

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
Penicillin
Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....

. Soil
Soil
Soil is a natural body consisting of layers of mineral constituents of variable thicknesses, which differ from the parent materials in their morphological, physical, chemical, and mineralogical characteristics...

 and water samples were collected from all over the world in order to study new bacterial or fungal strains
Strain (biology)
In biology, a strain is a low-level taxonomic rank used in three related ways.-Microbiology and virology:A strain is a genetic variant or subtype of a micro-organism . For example, a "flu strain" is a certain biological form of the influenza or "flu" virus...

, leading to an impressive arsenal of antibacterial agents such as the cephalosporins, tetracyclines, aminoglycosides, rifamycins, and chloramphenicol
Chloramphenicol
Chloramphenicol is a bacteriostatic antimicrobial that became available in 1949. It is considered a prototypical broad-spectrum antibiotic, alongside the tetracyclines, and as it is both cheap and easy to manufacture it is frequently found as a drug of choice in the third world.Chloramphenicol is...

.

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
Medicine
Medicine is the science and art of healing. It encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness....

. For example, asperlicin
Asperlicin
Asperlicin is a mycotoxin, derived from the fungus Aspergillus alliaceus. It acts as a selective antagonist for the cholecystokinin receptor CCKA, and has been used as a lead compound for the development of a number of novel CCKA antagonists with potential clinical applications....

 - isolated from Aspergillus alliaceus - is a novel antagonist of a peptide hormone
Peptide hormone
Peptide hormones are a class of peptides that are secreted into the blood stream and have endocrine functions in living animals.Like other proteins, peptide hormones are synthesized in cells from amino acids according to an mRNA template, which is itself synthesized from a DNA template inside the...

 called cholecystokinin
Cholecystokinin
Cholecystokinin is a peptide hormone of the gastrointestinal system responsible for stimulating the digestion of fat and protein...

 (CCK) which is involved in the control of appetite
Appetite
The appetite is the desire to eat food, felt as hunger. Appetite exists in all higher life-forms, and serves to regulate adequate energy intake to maintain metabolic needs. It is regulated by a close interplay between the digestive tract, adipose tissue and the brain. Decreased desire to eat is...

. CCK also acts as a neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...

 in the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...

 and is thought to be involved in panic attacks. Analogues of asperlicin may therefore have potential in treating anxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

. Other examples include the fungal metabolite lovastatin
Lovastatin
Lovastatin is a member of the drug class of statins, used for lowering cholesterol in those with hypercholesterolemia and so preventing cardiovascular disease...

, which was the lead compound for a series of drugs that lower cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...

 levels, and another fungal metabolite called ciclosporin
Ciclosporin
Ciclosporin , cyclosporine , cyclosporin , or cyclosporin A is an immunosuppressant drug widely used in post-allogeneic organ transplant to reduce the activity of the immune system, and therefore the risk of organ rejection...

 which is used to suppress the immune response after transplantation operations
Organ transplant
Organ transplantation is the moving of an organ from one body to another or from a donor site on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative medicine is allowing scientists and engineers to create organs to be...

.

The marine world


In recent years, there has been a great interest in finding lead compounds from marine
Marine (ocean)
Marine is an umbrella term. As an adjective it is usually applicable to things relating to the sea or ocean, such as marine biology, marine ecology and marine geology...

 sources. Coral
Coral
Corals are marine animals in class Anthozoa of phylum Cnidaria typically living in compact colonies of many identical individual "polyps". The group includes the important reef builders that inhabit tropical oceans and secrete calcium carbonate to form a hard skeleton.A coral "head" is a colony of...

, sponges
Sea sponge
Sponges are animals of the phylum Porifera . Their bodies consist of jelly-like mesohyl sandwiched between two thin layers of cells. While all animals have unspecialized cells that can transform into specialized cells, sponges are unique in having some specialized cells, but can also have...

, fish
Fish
Fish are a paraphyletic group of organisms that consist of all gill-bearing aquatic vertebrate animals that lack limbs with digits. Included in this definition are the living hagfish, lampreys, and cartilaginous and bony fish, as well as various extinct related groups...

, and marine microorganisms have a wealth of biologically potent chemicals with interesting inflammatory
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...

, antiviral
Antiviral drug
Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses...

, 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
Discodermolide
-Discodermolide is a recently discovered polyketide natural product found to be a potent inhibitor of tumor cell growth. The molecule's carbon skeleton is made up of eight polypropionate and four acetate units with 13 stereocenters.-History:...

, bryostatins, dolostatins, and cephalostatins.

Animal sources


Animal
Animal
Animals are a major group of multicellular, eukaryotic organisms of the kingdom Animalia or Metazoa. Their body plan eventually becomes fixed as they develop, although some undergo a process of metamorphosis later on in their life. Most animals are motile, meaning they can move spontaneously and...

s can sometimes be a source of new lead compounds. For example, a series of antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...

 peptide
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...

s were extracted from the skin of the African clawed frog
African clawed frog
The African clawed frog is a species of South African aquatic frog of the genus Xenopus. Its name is derived from the three short claws on each hind foot, which it uses to tear apart its food...

 and a potent analgesic
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....

 compound called epibatidine
Epibatidine
Epibatidine is an alkaloid found on the skin of the endangered Ecuadorian frog, Epipedobates tricolor. These frogs, like other poison dart frogs, are best known for their ability to sequester poisons from their prey and secrete these poisons onto their backs. Many Amerindian tribes would swipe the...

 was obtained from the skin extracts of the Ecuadorian poison frog.

Venoms and toxins


Venoms and toxins from animals, plants, snakes, spider
Spider
Spiders are air-breathing arthropods that have eight legs, and chelicerae with fangs that inject venom. They are the largest order of arachnids and rank seventh in total species diversity among all other groups of organisms...

s, scorpion
Scorpion
Scorpions are predatory arthropod animals of the order Scorpiones within the class Arachnida. They have eight legs and are easily recognized by the pair of grasping claws and the narrow, segmented tail, often carried in a characteristic forward curve over the back, ending with a venomous stinger...

s, insect
Insect
Insects are a class of living creatures within the arthropods that have a chitinous exoskeleton, a three-part body , three pairs of jointed legs, compound eyes, and two antennae...

s, and microorganism
Microorganism
A microorganism or microbe is a microscopic organism that comprises either a single cell , cell clusters, or no cell at all...

s 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
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...

, ion channel
Ion channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...

s, and enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

s. Many of these toxins are polypeptides (e.g. α-bungarotoxin from cobra
Cobra
Cobra is a venomous snake belonging to the family Elapidae. However, not all snakes commonly referred to as cobras are of the same genus, or even of the same family. The name is short for cobra capo or capa Snake, which is Portuguese for "snake with hood", or "hood-snake"...

s). However, non-peptide toxins such as tetrodotoxin
Tetrodotoxin
Tetrodotoxin, also known as "tetrodox" and frequently abbreviated as TTX, sometimes colloquially referred to as "zombie powder" by those who practice Vodou, is a potent neurotoxin with no known antidote. There have been successful tests of a possible antidote in mice, but further tests must be...

 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
Antihypertensive
The antihypertensives are a class of drugs that are used to treat hypertension . Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34%, of ischaemic heart disease by 21%, and reduce the likelihood of dementia, heart failure, and mortality from...

 agents cilazapril
Cilazapril
Cilazapril is a pyridazine angiotensin-converting enzyme inhibitor used for the treatment of hypertension and congestive heart failure. It is branded as Inhibace in Canada, Zapril in New Zealand, Vascace and Dynorm in Europe...

 and captopril
Captopril
Captopril is an angiotensin-converting enzyme inhibitor used for the treatment of hypertension and some types of congestive heart failure. Captopril was the first ACE inhibitor developed and was considered a breakthrough both because of its novel mechanism of action and also because of the...

.

The neurotoxins from Clostridium botulinum
Clostridium botulinum
Clostridium botulinum is a Gram-positive, rod-shaped bacterium that produces several toxins. The best known are its neurotoxins, subdivided in types A-G, that cause the flaccid muscular paralysis seen in botulism. It is also the main paralytic agent in botox. C. botulinum is an anaerobic...

are responsible for serious food poisoning (botulism
Botulism
Botulism also known as botulinus intoxication is a rare but serious paralytic illness caused by botulinum toxin which is metabolic waste produced under anaerobic conditions by the bacterium Clostridium botulinum, and affecting a wide range of mammals, birds and fish...

), but they have a clinical use as well. They can be injected into specific muscle
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...

s (such as those controlling the eyelid
Eyelid
An eyelid is a thin fold of skin that covers and protects an eye. With the exception of the prepuce and the labia minora, it has the thinnest skin of the whole body. The levator palpebrae superioris muscle retracts the eyelid to "open" the eye. This can be either voluntarily or involuntarily...

) to prevent muscle spasm. These toxins prevent cholinergic
Cholinergic
The word choline generally refers to the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation. Found in most animal tissues, choline is a primary component of the neurotransmitter acetylcholine and functions with inositol as a basic constituent of lecithin...

 transmission and could well prove a lead for the development of novel anticholinergic
Anticholinergic
An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. An example of an anticholinergic is dicycloverine, and the classic example is atropine....

 drugs.

Traditional Medicine


In the past, traditional peoples or ancient civilizations depended greatly on local flora
Flora
Flora is the plant life occurring in a particular region or time, generally the naturally occurring or indigenous—native plant life. The corresponding term for animals is fauna.-Etymology:...

 and fauna
Fauna
Fauna or faunæ is all of the animal life of any particular region or time. The corresponding term for plants is flora.Zoologists and paleontologists use fauna to refer to a typical collection of animals found in a specific time or place, e.g. the "Sonoran Desert fauna" or the "Burgess shale fauna"...

 for their survival. They would experiment with various berries, leaves
Leaves
-History:Vocalist Arnar Gudjonsson was formerly the guitarist with Mower, and he was joined by Hallur Hallsson , Arnar Ólafsson , Bjarni Grímsson , and Andri Ásgrímsson . Late in 2001 they played with Emiliana Torrini and drew early praise from the New York Times...

, root
Root
In vascular plants, the root is the organ of a plant that typically lies below the surface of the soil. This is not always the case, however, since a root can also be aerial or aerating . Furthermore, a stem normally occurring below ground is not exceptional either...

s, 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
Placebo effect
Placebo effect may refer to:* Placebo effect, the tendency of any medication or treatment, even an inert or ineffective one, to exhibit results simply because the recipient believes that it will work...

, 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
Traditional Chinese medicine
Traditional Chinese Medicine refers to a broad range of medicine practices sharing common theoretical concepts which have been developed in China and are based on a tradition of more than 2,000 years, including various forms of herbal medicine, acupuncture, massage , exercise , and dietary therapy...

 or Ayurveda
Ayurveda
Ayurveda or ayurvedic medicine is a system of traditional medicine native to India and a form of alternative medicine. In Sanskrit, words , meaning "longevity", and , meaning "knowledge" or "science". The earliest literature on Indian medical practice appeared during the Vedic period in India,...

 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
Ethnobotany
Ethnobotany is the scientific study of the relationships that exist between people and plants....

 can give clues as to which plants might be worth studying in more detail. Rhubarb
Rhubarb
Rhubarb is a group of plants that belong to the genus Rheum in the family Polygonaceae. They are herbaceous perennial plants growing from short, thick rhizomes. They have large leaves that are somewhat triangular-shaped with long fleshy petioles...

 root has been used as a purgative for many centuries. In China
China
Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...

, 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.) The most significant chemicals in rhubarb root are anthraquinones, which were used as the lead compounds in the design of the laxative
Laxative
Laxatives are foods, compounds, or drugs taken to induce bowel movements or to loosen the stool, most often taken to treat constipation. Certain stimulant, lubricant, and saline laxatives are used to evacuate the colon for rectal and/or bowel examinations, and may be supplemented by enemas under...

 dantron
Dantron
1,8-Dihydroxyanthraquinone is an organic substance with formula , formally derived from anthraquinone by the replacement of two hydrogen atoms by hydroxyl groups...

.

Insects have also gained recent attention as valuable sources of natural products and their use in traditional medicine has been reviewed.

The extensive records of Chinese medicine about response to Artemisia preparations for malaria also provided the clue to the novel antimalarial drug artemisinin
Artemisinin
Artemisinin , also known as Qinghaosu , and its derivatives are a group of drugs that possess the most rapid action of all current drugs against falciparum malaria. Treatments containing an artemisinin derivative are now standard treatment worldwide for falciparum malaria...

. The therapeutic properties of the opium poppy
Opium poppy
Opium poppy, Papaver somniferum, is the species of plant from which opium and poppy seeds are extracted. Opium is the source of many opiates, including morphine , thebaine, codeine, papaverine, and noscapine...

 (active principle morphine
Morphine
Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...

) were known in Ancient Egypt
Ancient Egypt
Ancient Egypt was an ancient civilization of Northeastern Africa, concentrated along the lower reaches of the Nile River in what is now the modern country of Egypt. Egyptian civilization coalesced around 3150 BC with the political unification of Upper and Lower Egypt under the first pharaoh...

, were those of the Solanaceae
Solanaceae
Solanaceae are a family of flowering plants that include a number of important agricultural crops as well as many toxic plants. The name of the family comes from the Latin Solanum "the nightshade plant", but the further etymology of that word is unclear...

plants in ancient Greece
Ancient Greece
Ancient Greece is a civilization belonging to a period of Greek history that lasted from the Archaic period of the 8th to 6th centuries BC to the end of antiquity. Immediately following this period was the beginning of the Early Middle Ages and the Byzantine era. Included in Ancient Greece is the...

 (active principles atropine
Atropine
Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade , Jimson weed , mandrake and other plants of the family Solanaceae. It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects...

 and hyoscine). The snakeroot
Snakeroot (disambiguation)
Snakeroot may refer to different plant taxa that have been used as a folk remedy against snakebites:* Ageratina – a genus with species native to the warm and temperate Americas* Certain plants in the temperate Northern Hemisphere genus Eupatorium...

 plant was well regarded in India
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...

 (active principle reserpine
Reserpine
Reserpine is an indole alkaloid antipsychotic and antihypertensive drug that has been used for the control of high blood pressure and for the relief of psychotic symptoms, although because of the development of better drugs for these purposes and because of its numerous side-effects, it is rarely...

), and herbalists in medieval England used extracts from the willow tree(salicin) and foxglove (active principle digitalis
Digitalis
Digitalis is a genus of about 20 species of herbaceous perennials, shrubs, and biennials that are commonly called foxgloves. This genus was traditionally placed in the figwort family Scrophulariaceae, but recent reviews of phylogenetic research have placed it in the much enlarged family...

 - a mixture of compounds such as digitoxin
Digitoxin
Digitoxin is a cardiac glycoside. It has similar structure and effects to digoxin . Unlike digoxin , it is eliminated via the liver, so could be used in patients with poor or erratic kidney function. However, it is now rarely used in current Western medical practice...

, digitonin
Digitonin
Digitonin is a glycoside obtained from Digitalis purpurea; the aglycone is digitogenin, a spirostan steroid. Used as a detergent, it effectively water-solubilizes lipids...

, digitalin). The Aztec
Aztec
The Aztec people were certain ethnic groups of central Mexico, particularly those groups who spoke the Nahuatl language and who dominated large parts of Mesoamerica in the 14th, 15th and 16th centuries, a period referred to as the late post-classic period in Mesoamerican chronology.Aztec is the...

 and Mayan
Maya civilization
The Maya is a Mesoamerican civilization, noted for the only known fully developed written language of the pre-Columbian Americas, as well as for its art, architecture, and mathematical and astronomical systems. Initially established during the Pre-Classic period The Maya is a Mesoamerican...

 cultures of Mesoamerica
Mesoamerica
Mesoamerica is a region and culture area in the Americas, extending approximately from central Mexico to Belize, Guatemala, El Salvador, Honduras, Nicaragua, and Costa Rica, within which a number of pre-Columbian societies flourished before the Spanish colonization of the Americas in the 15th and...

 used extracts from a variety of bushes and trees including the ipecacuanha root (active principle emetine), coca
Coca
Coca, Erythroxylum coca, is a plant in the family Erythroxylaceae, native to western South America. The plant plays a significant role in many traditional Andean cultures...

 bush (active principle cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...

), and cinchona
Cinchona
Cinchona or Quina is a genus of about 38 species in the family Rubiaceae, native to tropical South America. They are large shrubs or small trees growing 5–15 metres in height with evergreen foliage. The leaves are opposite, rounded to lanceolate and 10–40 cm long. The flowers are white, pink...

 bark (active principle quinine
Quinine
Quinine is a natural white crystalline alkaloid having antipyretic , antimalarial, analgesic , anti-inflammatory properties and a bitter taste. It is a stereoisomer of quinidine which, unlike quinine, is an anti-arrhythmic...

).

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
Medicine man
"Medicine man" or "Medicine woman" are English terms used to describe traditional healers and spiritual leaders among Native American and other indigenous or aboriginal peoples...

 - sharing their rituals while gaining knowledge. They responded to his inquiries in kind, leading to new medicines. On the other hand Cherokee
Cherokee
The Cherokee are a Native American people historically settled in the Southeastern United States . Linguistically, they are part of the Iroquoian language family...

 herbalist David Winston
David Winston
David Winston RH is an American herbalist and ethnobotanist. He has been in practice and teaching since 1977 and has written several books on the subject. He works in the Cherokee, Chinese and the Western eclectic herbal traditions...

 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. The issue of rights to medicine derived from native plants used and frequently cultivated by native healers complicates this 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 much on the structure, stability, and quantity of the compound. For example, Alexander Fleming
Alexander Fleming
Sir Alexander Fleming was a Scottish biologist and pharmacologist. He wrote many articles on bacteriology, immunology, and chemotherapy...

 recognized the antibiotic qualities of penicillin
Penicillin
Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....

 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
Aqueous solution
An aqueous solution is a solution in which the solvent is water. It is usually shown in chemical equations by appending aq to the relevant formula, such as NaCl. The word aqueous means pertaining to, related to, similar to, or dissolved in water...

, 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
Freeze drying
Freeze-drying is a dehydration process typically used to preserve a perishable material or make the material more convenient for transport...

 and chromatography
Chromatography
Chromatography is the collective term for a set of laboratory techniques for the separation of mixtures....

 that the successful isolation and purification of penicillin and other natural products became feasible.

Synthesis


Not all natural products can be fully synthesized
Total synthesis
In organic chemistry, a total synthesis is, in principle, the complete chemical synthesis of complex organic molecules from simpler pieces, usually without the aid of biological processes. In practice, these simpler pieces are commercially available in bulk and semi-bulk quantities, and are often...

 and many natural products have very complex structures
Chemical structure
A chemical structure includes molecular geometry, electronic structure and crystal structure of molecules. Molecular geometry refers to the spatial arrangement of atoms in a molecule and the chemical bonds that hold the atoms together. Molecular geometry can range from the very simple, such as...

 that are too difficult and expensive to synthesize on an industrial scale. These include drugs such as penicillin
Penicillin
Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....

, morphine
Morphine
Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...

, and paclitaxel
Paclitaxel
Paclitaxel is a mitotic inhibitor used in cancer chemotherapy. It was discovered in a U.S. National Cancer Institute program at the Research Triangle Institute in 1967 when Monroe E. Wall and Mansukh C. Wani isolated it from the bark of the Pacific yew tree, Taxus brevifolia and named it taxol...

 (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. 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.


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
Taxus brevifolia
Taxus brevifolia is a conifer native to the Pacific Northwest of North America. It ranges from southernmost Alaska south to central California, mostly in the Pacific Coast Ranges, but with an isolated disjunct population in southeast British Columbia, most notably occurring on Zuckerberg Island...

, then carrying out a four-stage synthesis.

See also

  • List of Natural Product Drugs
  • Ayurveda
    Ayurveda
    Ayurveda or ayurvedic medicine is a system of traditional medicine native to India and a form of alternative medicine. In Sanskrit, words , meaning "longevity", and , meaning "knowledge" or "science". The earliest literature on Indian medical practice appeared during the Vedic period in India,...

  • Chinese medicine
  • Ethnobotany
    Ethnobotany
    Ethnobotany is the scientific study of the relationships that exist between people and plants....

  • Journal of Natural Products
    Journal of Natural Products
    The Journal of Natural Products is a peer-reviewed scientific journal, co-published by the American Society of Pharmacognosy and the American Chemical Society.. The editor in chief is A. Douglas Kinghorn .- History :...

  • Pharmacognosy
    Pharmacognosy
    Pharmacognosy is the study of medicines derived from natural sources. The American Society of Pharmacognosy defines pharmacognosy as "the study of the physical, chemical, biochemical and biological properties of drugs, drug substances or potential drugs or drug substances of natural origin as well...

  • Phytotherapy
    Phytotherapy
    Phytotherapy is the study of the use of extracts from natural origin as medicines or health-promoting agents.Traditional phytotherapy is often used as synonym for herbalism and regarded as "alternative medicine" by much of Western medicine, although effects of many substances found in plants have...

  • Secondary metabolite
    Secondary metabolite
    Secondary metabolites are organic compounds that are not directly involved in the normal growth, development, or reproduction of an organism. Unlike primary metabolites, absence of secondary metabolities does not result in immediate death, but rather in long-term impairment of the organism's...


External links


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