Metabolites of the plant cell

Secondary metabolites

Metabolites of the plant cell

Primary metabolites they derive directly from the plant cell metabolism; they are needful for the cell survival.

Secondary metabolites organic compounds synthesized from primary metabolites; they are not needful for the cell survival, but contribute to the survival of the whole organism.

Metabolites of the plant cell

Primary metabolites Carbohydrates Lipids Proteins Organic acids Vitamins Chlorophylls Secondary metabolites Glycosides Phenolic compounds Terpenoids Alkaloids

Secondary metabolites
Once believed waste products of plant metabolism. Nowdays considered very important for the survival and propagation of plants. Ecological mediators: they show activity towards other living organisms; they are the product of environmental pressure on plant genome. They show toxicity not only for the plant itself, but also for pathogens, parasites, herbivores so that their main role is in the plant defense. Often characteristics of the species or genus to which the plant belongs to; they are used as chemotaxonomic markers. They are produced in a specific organ, tissue or type of cell during a specific stage; however, they are stored in different organs or tissues. They are not needful to cell development, but contribute to developmemnt of whole plant organism.

Secondary metabolites

Secondary metabolites
Main functions: Regulation of plant development during the biological cycle. Pollen and seed dispersion. Deterrent products assuring passive protection; they make plant unattractive to herbivores. Toxic products causing poisoning leading to death. Reaction products (active protection). Inhibition products of germination and development of plant competitors (allelopathia). Protection against sunlight.

Production of secondary metabolites replaces the lack of immune system and of movement as defense strategy. Plant can only adopt mechanical (formation of barriers) or chemical (active or passive) defense.

Secondary metabolites
25% of drugs currently used are from natural sources

in the last 25 years, about 70% of marketed drugs is indirectly derived from plant biodiversity

Secondary metabolites

Secondary metabolites
Alkaloids
10000 compounds

Terpenoids
22000 compounds

Phenolic compounds
Flavonoids ( 4000 compounds) Tannins Lignins Lignans Coumarins Naphthoquinones Anthraquinones Phloroglucinols Cannabinoids Salicylic acid

Morphine Cocaine Caffeine Nicotine Atropine Quinine Vincristine Vinblastine Strychnine Ephedrine

Essential oils Cardiac glycosides Resins Taxol Ginkgolides Steroids Saponins Iridoids Rubber

GLYCOSIDES

Glycosides
They derive from the bond between an organic molecule (called aglycone) and a sugar unit (glycone); in the case the latter would be glucose the compound is called glucoside and the sugar unit aglucone, respectively. They are solid, bitter compounds, easily hydrolyzed by enzymes or in the presence of an acidic environment. They are numerous in plants, and belong to the different secondary metabolites groups. Formation of a glycoside lead to a better bioavailability, stability and hydrophilicity for many substances that are normally liphophilic and highly reactive. Glycosides are stored in vacuole, protected from hydrolytic enzymes of cytoplasm. Glycosides are grouped on the basis of aglycone or type of bond between constituent parts (O-glycosides, C-glycosides, S-glycosides, N-glycosides). Biological activity depends on aglycone, while sugar unit modulates the intensity of action, and influences solubility and toxicity of the whole molecule.

Glycosides
glycosidation

aglycone
glycone

glycoside

glycosidase

Glycosides are formed through condensation

Glycosides
Glycosides-containing plants defend themselves against herbivores becoming less attractive or palatable. Many glycosides are extremely active compounds, but toxic at the same time (e.g. digitoxin). Some glycosides are used in the preparation of bitter beverages as appetite stimulant and digestive. Plant drugs containing high levels of glycosides must be dried rapidly and protected from moisture in order to avoid hydrolytic processes.

Glycosides
They are classified on the basis of the pharmacological activity or of the chemical structure of aglycone.

anthocyanosides (e.g. blueberry, currant). anthraquinone glycosides (e.g. aloe, buckthorn, senna, rhubarb). cardiac glycosides (e.g. digitalis, strophanthus, lily of the valley,
squill). cyanogenic glycosides (e.g. almond, cherry laurel, cherry, apricot). coumarinic glycosides (e.g. bergamot, sweet woodruff). flavonoid glycosides (e.g. hyssop, liquorice). hydroquinone glycosides (e.g. arbutus). iridoid glycosides (e.g. plantain, devils claw). salicylic glycosides (e.g. white willow, poplar). saponosides or saponins (e.g. liquorice, horse chestnut). sulphur glycosides (e.g. black and white mustard).

Glycosides

Glucosinolates , typical of Brassicaceae, are glycosides containing at least one atom of S; they are responsible for the characteristic odour releasing from these plants after hydrolysis. They are composed of glucose, a sulphur group and an aglycone; they originated from sulphur amino acids.

Glycosides
Glucosinolates occur in seeds of black and white mustard (sinigrin e sinalbin), and are used to prepare the namesake sauce (mustard). In diet, a long use of them is believed to be chemiopreventive against several types of cancer. The main constituent of fresh garlic is a sulphur compound (alliin) which, when hydrolysed, forms diallyl disulphide, responsible for the strong odour of garlic.

Phenolic compounds
Large group of widespread molecules having in common the presence of a phenolic group (1 C6 aromatic ring linked to a -OH hydroxyl group) that gives at the same time a high chemical reactivity and stability. They derive from different biosynthetic pathways (shikimic acid, acetic acid or both). Although their ecological role is not completely understood, it seems that they are involved in the plant defense and allelopathia. They are produces in almost all higher plants, occurring in all parts (e.g. roots, stems, leaves, flowers, fruits). They are the most studied secondary metabolites from a pharmacological point of view; they exhert many biological activities like antioxidant, antiplatelet, vasoprotective, anticancer, antimutagenic, antifungal, antibacterial, etc.).

Phenolic compounds
They comprise: Lignans Flavonoids Tannins Naphtoquinones Anthraquinones Phloroglucinols Coumarins Salicylic acid Lignins

Phenolic compounds

Lignans derive from the condensation of 2 phenylpropanoid units (C6C3). In plants they play a defensive role having antibacterial and antifungal activity. They possess also antimitotic activity so that some their hemisynthetic derivatives are used as anticancer agents. Their use as a food (e.g. linseed seeds) is recommended due to their chemopreventive effects.

Phenolic compounds

Flavonoids are widespread in plants; they derive from different biosynthetic pathways (mevalonate and shikimic acid). They represent the largest group of phenolic compounds (4000 compounds) studied. They are an oxygenated heterocycle composed of 2 aromatic rings linked by a C3-bridge. They are classified on the base of degree of oxidation of the central pyran.

Phenolic compounds
Anthocyanines or anthocyanosides are glycosides responsible for the red, pink, purple, blue colour of flowers, fruits and leaves.The aglycone obtained by hydrolysis are called anthocyanidines. Flavones and flavonols are the most widespread in the group; they give yellow and orange colour or colorless. Catechins are abundant in green tea, coffee and cocoa. Flavonoids act as signals to attract animal and insect pollinators, defend plant against UV radiations (they absorb in the UV-B region), and are involved in the plant interaction with other organisms (e.g. symbiotic bacteria of roots, pathogens, etc.).

catechins

carotenoids

Phenolic compounds
Flavonoids are water soluble pigments occurring in the vacuole of plant cells where they are present as glycosides.

anthocyanins

Phenolic compounds
Red to blue colours of flowers, fruits and leaves are due to anthocyanines which are water soluble and dissolved as vacuolar inclusions. Red colour of leaves during autumn is due to anthocyanines; they are produced as a result of low temperature and are highlighted when leaves stop chlorophyll production. In anthocyanines-lacking leaves, chlorophyll degradation highlights the yellow-orange colour due to carotenoids which are inclused in chloroplasts and chromoplasts.

Phenolic compounds
Flavonoids showed various pharmacological activities:
Vasoprotective (increase of strenght and decrease of permeability of capillaries) antiplatelet enzyme inhibition antinflammatory antispasmodic diuretic hypocholesterolemic antibacterial antiviral anticancer

Flavonoids are very used in Europe to make phytoterapics employed in the treatment of minor circulatory diseases.

Phenolic compounds
Tannins are polyphenols with high molecular weight (500-6000 dalton), capable of linking with sugar and proteins. They are substances with astringent properties, whose principal function appears to be to render plant tissues unpalatable to herbivores. Widespread in plants and in food of plant origin, in particular in fruits, legume seeds, cereal grains and different beverages (e.g. wine, tea, cocoa etc.). They have an astringent taste, give a blue or green colour with iron salts and are precipitated from water solution by proteins and alkaloids. Once used to treat hides to make leather owing to their properties to denature skin proteins. They are divided in hydrolysable or gallotannins (sugar esters of phenolic acids;origin from shikimic acid; when hydrolyzed they give gallic acid, or other phenolic acids), and condensed tannins or proanthocyanidins (polymer of flavonol derivatives, not hydrolysed).

Phenolic compounds

Proanthocyanidins (PAs) are far more common in our diet. They are polymers made of elementary flavan-3-ol units. A key feature of PAs is that they yield anthocyanidins upon heating in acidic media, hence their name.

Phenolic compounds
Tannins are stored mainly in vacuole (sometimes in cell wall). They are abundant in bark of Dicotyledones, leaves (e.g. tea) and immature fruits. They have astringent taste and reduce digeribility of food proteins. Used topically, they waterproof external layers of skin exherting vasoncostrictive effect and improve cicatrization after wounds and burns. Used internally as anti-diarrheic, antibacterial and antifungal. Hydrolisable tannins have antioxidant activity. At industrial level, they are used as mordants in the textile field, and for the clarification of wines, beers and liquors.

Phenolic compounds
Together with flavonols and resveratrol (a stilbene), tannins are abundant in red wine to which they attribute the preventive effect against cardiovascular diseases and cancer as evidenced by epidemiologic studies performed on French eating habits. Because of their antioxidant properties (e.g. EGCG, epigallocatechin gallate of green tea), they slow aging.

resveratrol

Phenolic compounds
Naphtoquinones are composed of the aromatic bicyclic system of naphtalene. They are restricted to a few families (e.g. roots of Borraginaceae). They have wound healing, anticancer, antinflammatory and antimicrobial activities. At food level, they are used to colour sausage skins and as inks for making food (alkannin). At cosmetic level, they are used as hair colorants (lawsone, main constituent of henna, and juglone from the husk of walnut).
OH O

OH

OH

alkannin
O OH

lawsone
OH O

Juglans regia

juglone

Alkanna tinctoria

Lawsonia inermis

Phenolic compounds
Anthraquinones are polyphenols derived from polymerization of acetyl CoA units (polyketides); they are glycosides with an aglycone composed of a tricyclic aromatic system derived from anthracene. They are found in bark, rhizomes, leaves and leaf juice of buckthorn, cascara, rhubarb, senna and aloe, respectively. They induce intestinal peristalsis acting as laxative. At low doses they are stomachic being employed in the liquor industry.

Phenolic compounds
Hypericin, contained in th black nodules of top flowering aerial parts of Hypericum perforatum (St. Johns wort) and other species of the genus Hypericum, is an anthraquinone dimer (naphtodianthrone), with antidepressive, antiviral, antimicrobial and wound healing activity. Noteworthy is its photosensitizing activity.
HO HO

OH

OH

OH

OH

Hypericin

Hypericum perforatum

Phenolic compounds
Phloroglucinols are terpenophenols of complex structure, such as humulone and lupulone obtained from female inflorescences and bracts of hop; hop is used to give bitter notes to beer; it is added to malt before fermentation. Due to its bactericide activity, it is also a preservative of the beverage. Finally, hop has sedative activity.

humulone

lupulone

Humulus lupulus

Phenolic compounds
Hyperforin is a phloroglucinol derivative occurring in flowers of Hypericum perforatum and other Hypericum species. Currently, it is considered the main responsible for antidepressive activity of Hypericum extracts. It possesses also significant antibacterial activity.

Hypericum perforatum

Phenolic compounds
Cannabinoids, i.e. cannabinol, cannabidiol or CBD, tetrahydrocannabinol or THC) are terpeno-phenols occurring in the resin of glandular hairs of female inflorescences of cannabis (Cannabis sativa), an annual, dioecious herb, native to central Asia and widespread in Europe since Middle Ages where it was cultivated as fiber plant. In China and India it was used as analgesic and antiseptic for external use and as inebriant (it gives excitement, euphoria, hallucinations). Its therapeutic use was stopped as a result of discovery of negative effects of cannabinoids on CNS and spermatogenesis. Recently it was showed that THC reduces lung and breast cancer and leukemia in animal models. In addition, it decreases pain in terminal cancer patiens and it increases food intake in HIV patients without side effects.

Phenolic compounds
Citrus bergamia Melilotus officinalis Pastinaca sativa

Coumarins are bicyclic aromatic compounds synthesized from cinnamic acid (a phenylpropanoid in turn derived from shikimic acid) and occurring mainly in the family of Rutaceae, Apiaceae, Fabaceae and Poaceae. In plant they can act as phytoalexins. As their main activities: anticoagulant, antiplatelet, anti-edema photosensitizing (furanocoumarins are used in the treatment of psoriasis and vitiligo because of the near-UV absorption).

Phenolic compounds

Coumarins are divided in 4 groups, on the base of chemical nature of substituents or of the type of molecule to which they are linked: Hydroxycoumarins (with one or more hydroxyl groups; e.g. umbelliferone). Furanocoumarins (coumarin nucleus linked to a furan ring; e.g. bergaptene and psoralen). Piranocoumarins (coumarin nucleus linked to a piran ring; e.g. visnadine). Glycosidic coumarins (coumarin nucleus linked to a sugar).

Phenolic compounds

Salicylic acid is known from ages for its analgesic, antipyretic and antinflammatory activities. It is obtained from the bark of willow (Salix alba, Salix purpurea). Its acetylated derivative (acetylsalicylic acid) is the active compounds of aspirin. Recently its was found to induce in the plant the systemic acquired resistance (SAR) as a consequence of an attack of pathogens (e.g. bacteria, virus, fungi) so that the other not yet infected parts are protected against the same pathogen agents.

Phenolic compounds
Conversely to other phenolic compounds, lignins are accumulated in cell wall rather than in vacuole. They are polymer of 3 different kinds of phenylpropanoids: p-coumaryl alcohol, coniferyl alcohol, sinapyl alcohol. Lignins improve mechanical support (e.g. sclerenchyma) and waterproof cell wall facilitating the sap transport into xylem. Lignification had a main role in the evolution of terrestrial plants (e.g. increase of height and photosynthetic surface). Lignin may be produced also as a consequence of wounds or attacks of pathogens such as fungi and bacteria acting as a phytoalexin.

Phenolic compounds
Lignin is not produced in cytoplasm, but its precursors synthesized herein move to cell wall where they undergo polymerization. Lignin is composed of a polymer of phenylpropanoid units (C6C3) with the occurrence of some sugar residues. It may differ in composition depending on the species. Lignin is important not only at structural level, but also because is chemically inert and not digestible at all to herbivores, thus representing a first form of chemical defense.
phenylpropanoid precursors

Terpenoids
They are the most widespread metabolites in plants. They are composed of two or more C5 isoprene units. They follow the mevalonate pathway. They are classified on the basis of the number of isoprene units: monoterpenes (2 units), sesquiterpenes (3 units), diterpenes (4 units) etc. A same plant may synthesize different kinds of terpenoids during its biological cycle and in different organs. Isoprene is a 5 carbon compound emitted from leaves of many plants during photosynthesis and is a component of smog. It is produced in chloroplasts and it seems that it aids heat dispersion.

Terpenoids

Terpenoids consist of 2 or more isoprenes units or their derivatives.

Terpenoids
Isoprene rule: the carbon skeletons of terpenes are built up of isoprene units with a head to tail arrangment. The actual precursor isopenthyl pyroposphate (IPP) and the closely related compound dimethylallyl pyroposphate (DMAPP), both derived from mevalonic acid, are incorporated into the various terpenoid classes precursors.

Terpenoids
Monoterpenes Monoterpenes

Sesquiterpenes

Some examples of monoterpenes and sesquiterpenes. They may be linear or cyclic molecules or combinations of both.

Terpenoids
Essential oils are mixtures of highly volatile monoterpenes and sesquiterpenes giving the odour to plants (aromatic plants). Their main role is to attract pollinators, as defense against pathogen microorganisms, as allelopathic agents, to render plant unpalatable to herbivores, to reduce water loss through their evaporation. They are used in perfumery, cosmetics, liquor, as food additives and preservatives, and in pharmaceutical technology as flavour enhancers. They are obtained by steam distillation (or hydrodistillation) except those of citrus that are obtained by cold pressing.

Rosmarinus officinalis

Terpenoids

Most of essential oil constituents are dissolved in vacuole under glycosides, before moving to secretory structures such as glandular trichomes, and lysogen or schizogenic pockets. The richest sources of essential oils are: Asteraceae, Lamiaceae, Myrtaceae, Rosaceae, Rutaceae, Apiaceae, Pinaceae.

Terpenoids
Resins are secretion products of conifers, semifluid substances containing lowly volatile terpenes such as diterpenes (pimaric and abietic acids). They are produced into resin channels of wood of stem from which they come out as a consequence of an incision in the bark. They are also produced in needles. They have defensive functions, to protect against infections by stress-related pathogens. They become solid on exposure, are of characteristic odour, and water insoluble. From distillation of resins, is obtained turpentine, composed of volatile components such as -pinene which is used in therapy to treat respiratory diseases.

Terpenoids
Taxus baccata

Taxol, complex diterpene with anticancer activity obtained from the bark of Pacific yew (Taxus brevifolia). It reduces breast-ovarian cancers through perturbation of mitosis (it promotes microtubule assembly and inhibites disassembly). Taxol derivatives are obtained from European yew (Taxus baccata) from which taxol is currently synthesized.

Taxus brevifolia

Terpenoids
Ginkgo biloba

Ginkgolides are diterpenes with a particular structure in the plant kingdom. They are contained in the fan-shaped leaves of ginkgo (Ginkgo biloba), a living fossil (occurring since 200 million years ago) native to China, but cultivated all over the world. They are used in therapy to treat peripheral and brain circulatory insufficiency, dementia, and experimentally employed against Alzheimer disease.

Digitalis purpurea

Digitalis lanata

Terpenoids

Cardiac glycosides (known as cardenolides), poisonous terpenoids with steroid aglycone, are used in therapy to treat cardiac dysfunctions. The main representatives are digitoxigenin and digoxin which are obtained from the leaves of digitalis (Digitalis purpurea and D. lanata). In plants they act as a powerful poison serving as defense towards herbivores.

Terpenoids
Iridoids are non volatile monoterpenes of complex structure, usually occurring as glycosides. They are often intermediates in the biosynthesis of alkaloids. The name derives from ants of the genus Iridomyrmex from which they were isolated for the first time. Those contained in the roots of gentian (secoiridoids such as amarogentin and gentiopicroside) are the most bitter natural compounds known to humans used to make liquors (they stimulate gastric secretion). Those contained in root and rhizomes of valerian (valepotriates) have sedative properties. Those contained in the tuberous roots of devils claw (harpagide, procumbide) are antiinflammatory agents.
Gentiana lutea

valtrato Valeriana officinalis

harpagide
Harpagophytum procumbens

Terpenoids
Triterpenes and steroids are complex molecules widely distributed in nature, all dervied from the hydrocarbon squalene (C30H50). Saponins are amphipathic glycosides widely diffused in plants and deriving the name from the soap-like foaming they produce when shaken in aqueous solutions. They are composed of one or more hydrophilic glycoside moieties combined with a lipophilic triterpene derivative which may be a steroid (usually in Monocotyledones) or a triterpene (in Dicotyledones) itself. They have haemolytic properties; in plants they exert antifungal activity. Saponins of horse chestnut and liquorice are used as anti-edema and antiinflammatory agents, respectively. Steroidal saponins (e.g. from Dioscorea) may be exploited by pharmaceutical industry to synthesize hormones used as contraceptive drugs.

Dioscorea sp.

Glycyrrhiza glabra

Aesculus hippocastanum

Terpenoids

Terpenoids
Carotenoids are yellow to orange pigments contained in chloroplasts and chromoplasts; they are composed of a long isoprenoid chain (they are tetraterpenes) with 2 hexagonal rings (opened or closed) to the ends. They are divided in carotenes (only C and H) and xanthophylls (with oxygenated functions).

Terpenoids
-carotene is a component indispensable for membrane fabrication, a potent antioxidant, and the primary source of vit. A for humans and animals. Carotenoids are water insoluble while they are soluble in organic solvents such as acetone and alcohol. They are abundant in tomatoes and carrots. They are used also in foodstuffs as colouring agents (e.g. crocin from saffron) and in liquor industry.

Terpenoids

Terpenoids
Rubber, is the largest terpenoid, composed of hundreds of isoprene units, exhibiting elasticity at room temperature. It is obtained from the latex of rubber tree (Hevea brasiliensis), a tropical plant belonging to Euphorbiaceae, by means of a V-like cut into the bark. Once employed as source of tires gum, it is nowdays used to make tourniquets, catheters, latex gloves etc.

Terpenoids
Other terpenoids playing important functions in plant cell are:

Chlorophyll constituents (phytol). Plant hormones (gibberellines, abscissic acid). Membrane components (sterols). Electron transporters (ubiquinone, plastoquinone).

Alkaloids
Alkaloids are derived from plants (20% of plant species) and have powerful pharmacological effects (mainly on CNS). They are importan drugs used in therapy. They are basic, nitrogenous, normally heterocyclic compounds of complex nature. They have bitter taste, colourless and odorless, solid at ordinary temperature. They are synthesized from amino acids. They are soluble in organic solvents. In plant cell they are stored in vacuole (never in cytoplasm or cell wall), where combined with organic acids they form water-soluble salts. Sometimes they are accumulated in extracellular spaces (e.g. laticiferous vessels). They occur in all plant parts, although generally one organ shows higher amounts respect to the others. Normally plants synthesize alkaloids in such an organ, then store them in another one. Generally, alkaloids occur as a mixture of molecules belonging to such a chemical group (of same biosynthetic origin); among them generally one compound is more abundant. Alkaloids are more abundant in Angiosperm Dicotyledones, less abundant in Monocotyledones, and sporadic in Gymnosperms. They occur in 20% of plants. Their function is uncertain, but in some species they confer a degree of protection against insect and herbivore attacks (due to their toxicity).

Alkaloids
They are classified on the basis of nature of heterocyclic ring, or of the biosynthetic origin. Exocyclic alkaloids (e.g. ephedrine). Indole alkaloids (e.g. strychnine, vincristine) Isoquinoline alkaloids (e.g. papaverine, emetine). Tropane alkaloids (e.g. atropine, hyoscyamine, cocaine). Piperidine alkaloids (e.g. coniine). Pyridine alkaloids (e.g. ricinine). Pyrrolidine alkaloids (e.g. nicotine). Purinic alkaloids (e.g. caffeine, theophylline, theobromine).

Alkaloids

Alkaloids

Papaver somniferum

Morphine, is the first identified alkaloid (1806), occurring in the immature capsule of opium poppy (Papaver somniferum). It is used in medicine as the most potent analgesic (pain relief) and cough suppressant. Its excessive use may give drug addiction (compulsive need to use substances in order to function normally).

Alkaloids
Erythroxylon coca

Cocaine, is obtained from the leaves of coca tree (Erythroxylon coca), a plant occurring on the eastern slopes of the Andes, mainly in Bolivia and Peru where indigenous used to chewed leaves to alleviate hunger and fatigue. However, smoke, sniff or inject intravenous cocaine may be destructive, leading to death. In therapy it was used as local anesthetic and simpaticomimetic.

Alkaloids

Coffea arabica

Camellia sinensis

Theobroma cacao

Caffeine occurs together other purinic alkaloids in seeds of coffee (Coffea arabica), cocoa (Teobroma cacao), guaran (Paullinia cupana), and cola (Cola nitida), and in leaves of tea (Camelia sinensis) and mate (Ilex paraguariensis). It is a stimulant, reducing fatigue and improving mind focusing. It is used as ingredient of anti-influenza drugs and in weight loss products since it acts on lipolysis. At food level, it is used as ingredient of beverages and energy drinks. It seems that caffeine defends against fungi and insects, and plays a role as allelopathic, inhibiting seed germination and plantlets of competitors.

Alkaloids
An American pharmacist, J.S. Pemberton, in 1886 invented an alcoholic beverage containing extracts from leaves of coca and seeds of cola, as a valuable brain tonic that would cure headaches, relieve exhaustion and calm nerves, then become analcoholic: the Coca Cola. At the beginning of 20th century the recipe was reformulated without psycotropic substances.

Cola nitida

Erythroxylon coca

Alkaloids
N N

nicotine

Nicotiana tabacum

Nicotine is a toxic alkaloid obtained from leaves of tobacco (Nicotiana tabacum). Nicotine is synthesized in roots and then stored in vacuole of mesophyll cells. It is a powerful insecticide and a protective agent against herbivore attacks; it may be produced also as a consequence of wounds acting as a phytoalexin.

Alkaloids
OH O

atropine

Atropine, contained in the leaves of belladonna (Atropa belladonna), is used as cardiac stimulant, to dilate the eye pupils and as antidote against muscarinic and nerve gas poisoning.

Alkaloids
N

O H OH N

quinine

Cinchona sp.

Quinine is contained in the bark of cinchona tree (Cinchona calysaia, C. succirubra, C. ledgeriana), a plant native to Peruvian Andes (1500-3000 m a.s.l.). It is used to treat malaria since it inhibites several strains of Plasmodium. At food level, the bark is used in the preparation of tonic water and liquors.

Alkaloids
Vincristine and Vinblastine are indole alkaloids contained in the aerial parts of vinca rosea (Catharanthus roseus), a perennial herb native to Madagascar, cultivated as ornamental elsewhere. They are used as anticancer drugs in the treatment of leukemia, lymphomas and lung cancer since they perturbate mitosis (they inhibite microtubule assembly).

Catharanthus roseus

Alkaloids
Chondrodendron tomentosum Strychnos nux-vomica

Alkaloids are powerful poisonous substances exploited by humans since ages. However, at low doses they may be used without causing damage. An example is strychnine, the poison par excellence; it is obtained from seeds of Strychnos nux-vomica; it is a stimulant of the nervous system and in large doses causes convulsions; at low doses is used as appetite stimulant due to its bitter taste.
Curare is a plant extract containing alkaloids (from bark of Chondrodendron tomentosum, seeds of Strychnos an others) that blocks the passage of nerve impulses causing paralysis and breathing causing asphyxiation. It is used by southern American Indians as an arrow poison for hunting. From it have been obtained the first drugs (e.g. tubocurarine) used in anesthesia to make possible surgery.

Ephedra sinica
NH

Alkaloids

OH

ephedrine

Ephedrine is a protoalkaloid obtained from young stems of ma-huang (Ephedra sinica, Gymnosperms), native to China where it is used to treat cold. It acts as a simpaticomimetic giving hypertension, tachycardia, vasoconstriction and broncodilation. It has also stimulant effects on CNS because of the structure similar to that of amphetamines. It used as bronchodilator agent of drugs to treat asthma and cold, and as a thermogenic and slimming drug in weight loss products.

PHYTOALEXINS

Antifungal or antiviral substances that are produced by plants in response to damage or infection (active defense). They may help to protect plant from diseases. Various secondary metabolites may be synthesized as phytoalexins.

CONSERVATION OF ACTIVE COMPOUNDS

Vacuole represents the main site for the storage of active compounds in medicinal plants. Their preservation is threatened when, during harvesting, plant structures are damaged causing enzymatic reactions. The simplest way to stop degradation of plant drugs is drying since it blocks enzymatic activity. For this reason medicinal plants are immediately dried after harvesting and stored in a dry environment, protected from moisture and light.

WHY PLANTS HAVE EFFECT ON HUMANS?

Secondary metabolites produced by plants are capable to interact with receptors of animals, insects, microorganisms, etc. by exherting biological effects. Nature of human receptors (proteic) is similar to those of targeted-organisms with which plant interact so that secondary metabolites are able to produce such an effect also on humans. As an example, plants secrete substances that mimic those naturally-produced by humans (e.g. morphine-enkefaline, ephedrine-noradrenaline, muscarine-acetylcoline, glycyrrhizine-aldosterone, etc.). In other cases, identical substances to those secreted by humans are found also in plants (e.g. nettle-histamine, spinach-insulin, coffee- purinic compounds, chamomile-benzodiazepine-like compounds).

Biosynthesis of secondary metabolites

Biosynthesis of secondary metabolites

Photosynthesis synthesizes a large amount of primary metabolites (e.g. carbohydrates). Glycolysis of primary metabolites (eg. glucose) produces C3 units of piruvic acid that may link to erythrose (glucose derivative) giving shikimc acid with a cyclic structure, or may lose one carbon atom giving acetyl-CoA. Shikimc acid and acetyl-CoA are intermediate products of biosynthetic pathways leading to different groups of secondary metabolites.

Biosynthetic pathways
ACETIC ACID SHIKIMIC ACID
Aromatic amino acids Alkaloids Phenolic compounds (phenylpropanoids, lignins, lignans, coumarins, phenolic acids, phenols, hydrolysable tannins)

CITRIC AND SUCCINIC ACID

Porphyrin ring of chlorophylls

POLYCHETIDES
Anthraquinones Fatty acids

MEVALONIC ACID
Terpenoids

MIXED PATHWAY
Flavonoids Condensed tannins