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Secondary metabolites, identification and types of secondary metabolites

Secondary metabolites, identification and types of secondary metabolites در ﻃﯽ ﺳﺎﻟﯿﺎن ﻃﻮﻻﻧﯽ، ﺑﺸﺮﯾﺖ از اﯾﻦ وﯾﮋﮔﯽ در ﮔﯿﺎﻫﺎن داروﯾﯽ در ﺻﻨﺎﯾﻊ ﻣﺨﺘﻠﻔﯽ ﻫﻢﭼﻮن ﺻﻨﻌﺘﯽ، داروﯾﯽ، ﺑﻬﺪاﺷﺘﯽ و ﺑﻬﺮه ﺟﺴﺘﻪ اﺳﺖ. ﺑﺮﺧﻼف ﻣﺘﺎﺑﻮﻟﯿﺖﻫﺎي اوﻟﯿﻪ، ﻫﻢﭼﻮن ﮐﺮﺑﻮﻫﯿﺪارتﻫﺎ، ﭘﺮوﺗﺌﯿﻦﻫﺎ و اﺳﯿﺪﻫﺎي ﻧﻮﮐﻠﺌﯿﮏ، ﻧﺒﻮد ﻣﺘﺎﺑﻮﻟﯿﺖﻫﺎي ﺛﺎﻧﻮﯾﻪ ﺑﻪ ﻣﺮگ ﻓﻮري ﻣﻮﺟﻮد ﻣﻨﺠﺮ ﻧﻤﯽﺷﻮد، اﻣﺎ ﻣﻤﮑﻦ اﺳﺖ در دراز ﻣﺪت ﺳﺒﺐ اﺧﺘﻼل در ﺑﻘﺎي ﻣﻮﺟﻮد زﻧﺪه، ﺑﺎروري ﯾﺎ وﯾﮋﮔﯽﻫﺎي ﻇﺎﻫﺮي آن ﮔﺮدد ﯾﺎ ﻣﻤﮑﻦ اﺳﺖ ﻫﯿﭻ ﺗﻐﯿﯿﺮ ﻣﺸﻬﻮدي را ﺳﺒﺐ ﻧﺸﻮد.

Because plants are not motile, they have evolved with a high degree of physiological flexibility to adapt to fluctuating external conditions. In addition, many plant species are dependent on animals for sexual reproduction and seed dispersal. Among the adaptive responses of plants to environmental stresses is the ability to synthesize many types of these chemical compounds.

As mentioned, secondary metabolites are not part of the cellular molecular structure, are found in small amounts and may
They have no obvious role in development and, if present, are found in certain tissues, organs or at certain stages of development. Their production may also be on a large scale or limited to a particular family or genus or even a particular species of plant.
Secondary metabolites are widely used in industrial products and in the manufacture of medicines, soaps, essential oils, dyes, gums, resins,
Rubber, seasonings for food and beverages, etc. are used. These compounds in the plant itself have important functions such as the function of hormones and growth regulators, elimination of microbial contamination, absorption of pollinators and also repel herbivores and insects, which thus reduces the damage to animals and insects and plants. Manufacturers help to survive in their ecosystem. Plants use these compounds, which belong to different chemical families, including alkaloids and flavonoids, to protect themselves against microbial attack, herbivores and ultraviolet radiation. Secondary metabolites also play a key role in the uptake of pollinating insects, especially anthocyanin pigments and terpenoids (and in other beneficial interactions with other organisms).

The need to study secondary metabolites

Metabolites or by-products, in addition to their complex biosynthetic pathways for production, also have complex structures, which has slowed their study. However, the high value of these compounds in industries such as medicine, necessitates the chemical study of these compounds. The study of secondary metabolites also enhances our understanding of biosynthesis and their activity.
It should be noted that the structure of these molecules is often too complex for fully efficient chemical synthesis. For this reason, despite the low concentration of these metabolites in plants, plants are still the only economically viable source for many of these valuable metabolites. On the other hand, the increasing tendency of human societies to use herbal medicines has increased the demand for active ingredients of medicinal plants. Despite many advances in the synthesis of synthetic plant active ingredients, due to the unknown and complexity of the chemical structure of most of them, the production of these compounds synthetically is difficult and requires a lot of money. As a result, so far there has been no significant success in the production of these valuable medicinal compounds, and extraction from plant sources is still the only economically viable source of these compounds.

Finally, studying and understanding these valuable compounds can help us invest more in our country’s native plants. For example, the compound noscapine is an anti-cancer agent that binds to tubulin filaments in the metaphase phase, stopping cell division and inducing apoptosis in cancer cells. This secondary metabolite is found in poppies and only in the genus Papaver, and to date Papaver somniferum is the only commercial source for the production of this valuable substance. On the other hand, due to the presence of two chiral carbons in its chemical structure, the chemical synthesis of noscapine is very time consuming and costly.
New studies show that Iranian poppy (L. bracteatum Papaver) also has noscapine biosynthetic genes and due to its perennial and adaptation to the Iranian climate, can be a good source for noscapin production in the country. It should be noted that the Iranian poppy plant has become very famous for its high codeine, but as mentioned, by studying other compounds in native species, we can introduce suitable sources for the production of such essential drugs.

Classification of secondary metabolites

The secondary metabolites are mainly composed of three classes of terpenoids which are about 25,000, alkaloids about 12,000, and phenolic
There are about 8,000 different compounds, but in addition to these metabolites, we can mention essential oils, flavonoids and other classes (Croteau 2000).

Terpenoids

Terpenoids are the most naturally occurring natural plant compounds. These compounds are due to the wide application that in
Industrial products, including spices, drugs, perfumes, insecticides, and antimicrobials, are commercially important. Due to their unique properties, terpenoids are used as biological materials in industry to produce heavy elastics, shock absorbers and Alex products such as surgical gloves.
Other examples of plant terpenoids of considerable economic value include the following:
Menthol is a monoterpenoid extracted from mint and is used in the flavoring industry.
Abetic acid, a deterpenoid isolated from rosin conifer used in the lacquer, varnishes and soap industries.
Artemisinin and taxol, which are used as antimalarial and anti-cancer drugs.
The term terpene refers to hydrocarbon molecules, while terpenoids refer to terpene molecules that have undergone subsequent changes. Terpenoids are the most abundant and diverse natural compounds known in plants. These valuable compounds also play many roles in the plant itself, including the protection of plants against vegetarians, the absorption of pollinators, the coexistence of plants with other organisms and the competition of plants with other plants.
Taxol is a very important cyclic diterpenoid extracted from the yew tree (Taxus brevifolia) in 1962.
The molecular structure of this compound was determined in 1971 by X-ray crystallography. This combination today as a
An important anticancer drug used in chemotherapy. The anti-cancer mechanism of this compound is such that by connecting to the subunits of microtubules, it prevents their polymerization, so during cell division, it prevents the proper separation of chromosomes and prevents cell growth by disrupting cell division.

Alkaloids

Alkaloids are compounds that have at least one nitrogen atom in a heterocyclic ring. These secondary metabolites play a predominantly defensive role and are sometimes used as sources for nitrogen storage in plants. Among the most important alkaloids are morphine and codeine.

The word alkaloid is adapted from the words alkali and ιδоо Greek word (Similarity) or ιδŵ meaning to appear. Basically
Substances that have an alkaline appearance are called. The root of the word alkali from the Arabic part al-qualja means plant ashes, which is synonymous with the English word potash. The word was first used in 1819 by W. Meissner. According to her, alkaloids are substances extracted from plants that react like alkalis.

The term was finally coined in 1822 when O. Jacobsen wrote and co-authored a complete paper on these compounds, “ter buch der chemieÖ A. Ladenburg’s Hand W.” This term is for all bases, organic matter, whether animal or not
Herbal and all artificially prepared materials are used. In other words, alkaloids with organic bases or organic alkalis
It is synonymous.

About 43 years later, A. Stoll introduced nitrogen-containing play compounds in plants as alkaloids. In 1959,
P. Karrer made the same definition in the journal Lehrbuch der organis chemie. In 1983, S.W. Pelletier declared that alkaloids were an organic ring compound containing nitrogen in a negative oxidation state whose distribution among living organisms was limited. None of these definitions are complete, and each has a fundamental flaw.
Today, however, alkaloids are more or less natural nitrogenous organic matter with a degree of alkalinity. This definition does not include pure amino acids, peptides, nucleic acids, and synthesized organic nitrogenous bases such as aniline. There are currently about 6,000 natural alkaloids. Today, 25% of commercial drugs are made from these compounds and their derivatives. Alkaloids are the most well-known natural compounds containing nitrogen. These compounds have a bitter taste and have a toxic effect on the cell membrane system, especially nerve cells. They act as an insecticide and are also very important in the pharmaceutical industry. Highly addictive compounds such as cocaine, morphine, nicotine, caffeine and THC or Tetra hydro cannabinol (marijuana) are in this group. Indole alkaloids are broad-spectrum secondary metabolites that have a wide variety of pharmacological activities. Indole alkaloids and their derivatives have been widely used in clinical trials. Including vinblastine, vincristine, computotsin, vindoline, reserpine and indoline. Extensive studies have shown the diverse biological activity of indole alkaloids from antibacterial activity to anti-inflammatory activity and anti-tumor activity. In addition, indole alkaloids from the marine environment are a promising and active group of biomolecules that cover biological, cytotoxic, antiviral, antiparasitic, and anti-inflammatory activities.

Flavonoids

The term flavonoid, in a broad sense, includes all plant pigments. The name flavon is derived from the Latin word flavus meaning yellow
Has been. About 4,000 types of flavonoids have been identified in higher plants, especially carnivores, of which more than 90 types of flavonoids are found in citrus and more than 30 species in the composite family. To date, no flavonoids have been reported in algae. Among the compounds
Phenols, flavonoids have all the functions of secondary metabolites in plants. Flavonoids are phenylpropanoid derivatives that have a 15-carbon structure. In most flavonoids, ring A is hydroxyl methadone or methyl hydroxyl, while ring B has one, two, or three hydroxyl agents. This difference is due to the origin of the two-ring biosynthesis. Ring A is derived from three dense acetic acid molecules and Ring B is derived from sugars in the schemic pathway.

Properties of flavonoids

Flavonoids cause color in flowers, fruits and sometimes leaves. They are also effective in pollination and fertility of plants due to their ability to attract insects. Flavonoids increase resistance to pathogens in plants and are also strong absorbers of ultraviolet light (340-250 nm). In the structure of sexual and vegetative organs, pollen grains have a positive effect on the action of genes and enzymes. It also causes some metal ions, such as iron and copper, to chelate. Flavonoids prevent oxidation by inhibiting catalyzed elements. Other properties of these materials include waste collection properties. Other properties of these materials include waste collection properties. Flavonoids are also used to treat hepatitis in China. 45% of citrus flavonoids specifically improve the absorption of vitamin C. Smokers and people under stress need a lot of vitamin C and citrus flavonoids. Citrus flavonoids can be used in combination to control smokers or in the form of ampoules for athletes.
Herbs such as yarrow, red walnut, ginkgo, thyme, thyme, chamomile, pomegranate, tea, hawthorn, bay leaf, clock flower, citrus, licorice are among the valuable sources of flavonoids. Phenolics These compounds are mainly derived from the schemic pathway of acid and aromatic amino acids. Because they are circular, they have the ability to receive and emit light and use this feature to identify them. These substances act as ionizing agents in the presence of a base and cause free radicals.
The materials of this group have different applications in different industries, including tannins in the leather industry
Participate. These compounds are also widely used in spices, and some substances in this group (vitamin E) have significant antioxidant activity. Identification of the target metabolite Undoubtedly the most important part in the discussion of metabolite engineering is the identification of metabolites. The properties of this compound can be studied by laboratory methods. Nowadays, considering that the structure of valuable compounds is available, it is possible to adapt the structure of the desired compound to the existing compounds and to guess the specific feature of this compound to some extent. For example, a compound that is thought to be an anti-cancer agent can be tested using laboratory methods with cells.
Studied cancer. Also, today, by studying the metabolic profile of a plant with methods such as MS-HPLC and MS -LC, the compounds in the plant were informed. Some of these compounds are isolated, such as taxol, which acts as an anti-cancer compound
Or artemisinin, which has anti-malarial activity, draws the attention of researchers to study the pathways
Biosynthesis of these compounds, as well as other compounds that may have strong pharmacological effects.
The role of metabolic studies in such research is twofold. Identify the temporal and spatial distribution of the metabolite in question that occurs by plant conditions or environmental changes, and second, identify other related compounds. These compounds can be identified as intermediates in these pathways. A combination of metabolic studies and studies related to genomics, transcriptomics and proteomics can help identify the biosynthetic pathways of these phytochemical compounds.
Make valuable. Methods for identifying secondary metabolites Given the value of secondary metabolites and the need to study them, a variety of laboratory methods have been introduced to study the structure of these compounds, some of which are studied in this study. Many of these methods are costly and time consuming in the first place, so one of the advantages of identifying the structure of secondary metabolites is the possibility of creating virtual libraries of information on these compounds. Hence, compounds can be studied with more cost-effective devices. Identification of the chemical structure also provides an opportunity to study the ligand-enzyme properties in vitro. Mass spectrometry One of the methods of studying chemical compounds is mass spectrometer, which involves separating one or more atomic ions based on mass to charge ratio (m / z) and measuring m / z and the frequency of ions in the gas phase. . More precisely, mass spectrometry examines the mass-to-charge ratio of molecules using electric and magnetic fields. This method is one of the most widely used methods in identifying metabolites. The main advantage of this technique is its high sensitivity. The main advantage of this technique is its high sensitivity.

 

Methods of studying valuable metabolites in plants

 

The two combined methods GC – MS and LC – MS are the most widely used. Gas mass chromatography, a widely used method in
Isolation and identification of volatile gas mixtures. The GC-MS consists of a combination of gas chromatography (to separate gas mixture components) and mass spectrometer (to identify components). Gas chromatography, like other chromatographic methods, consists of two moving and stationary phases. The stationary phase consists of an adsorbent solid (gas-solid chromatography) or a thin layer of a non-volatile liquid (gas-liquid chromatography), whose inner walls
Covers the column or on the surface of glass or metal bullets. The mobile phase consists of a gas, also called a carrier gas. The carrier gas must be an inert gas, so as not to react with the stationary phase, solvent or sample. For this reason, nitrogen or helium is usually used. Using this method to identify certain types of samples such as terpenoids and essential oils is very appropriate and practical. Also for some plant derivatives that are polar or those that have polar groups such as amino acids, sugars, natural acids, fatty acids and amines. This suggests that many compounds associated with primary metabolites are easily identifiable by this method. The ionization method in this method is more in the form of EI, which increases the accuracy of separation of ionic compounds to the device.

 

Plant metabolomics experiments using MS method

 

The LC-MS method is also one of the most widely used methods in studies related to metabolism in plants. The main method for ionization
In this technique, it is also API, which actually includes two methods, EI and APCI. These two methods do not need to evaporate
And therefore to study compounds with a heat-sensitive functional group, with unstable chemical infrastructure, with
High evaporation point and high molecular weight are suitable. In plants the LC-MS method is used to profile many secondary metabolites
Used to include phenylpropanoids, alkaloids and saponins.
Nuclear magnetic resonance spectroscopy
NMR, or nuclear magnetic resonance spectroscopy, is another popular method in metabolic studies. This method is mostly because it determines the atomic status of compounds, and is also able to identify metabolites that can not be detected by methods such as MS. With the help of NMR spectroscopy, accurate information about values ​​and identity can be obtained
Acquired metabolites in the extract as well as intracellular conditions (in vivo).

Chromatographic or standard columns are not required for NMR metabolite analysis. In this method, only the sample Hp should be considered
It was special because chemical shifts could be changed based on the pH of the sample. In order to control pH and possible errors, from
Buffers are used to control the pH. Other advantages of NMR over MS include non-destructive NMR,
Non-biased, very little, and the ability to identify anonymous complex compounds noted.
Medicinal Plants: Sources for Secondary Metabolites Undoubtedly, herbs are the most important and best source of secondary metabolites that have been recognized as valuable resources for generations. Sources for Secondary Metabolites Undoubtedly, herbs are the most important and best source of secondary metabolites that have been recognized as valuable resources for generations. Iran has been a region for the growth of many medicinal plants due to its different and compatible climate. Medicinal plants have a special value and importance in ensuring the health of communities, both in terms of treatment and prevention of diseases. This part of natural resources has a long history with human beings and is one of the most important sources of human food and medicine
They have been for generations. From a historical point of view, these plants have been of great importance in the development of societies and extensive research has been done to find natural herbal medicinal products and substances throughout history, but the important point is that only less than 10% of the world’s 250,000 plant species for more than A biological function has been identified and used. In other words, according to statistics published by the World Health Organization [2], only between 35,000 and 70,000 species of medicinal plants have been used at least once or more over time. Currently, 25% of existing drugs are of plant origin and 12% of drugs are made from microbial sources. The potential for the production of herbal medicines in nature is very high. These plants contain valuable compounds known as secondary metabolites.
Medicinal Plants Market in Iran and the World Today, many human societies seek to earn money and trade through medicinal plants containing valuable secondary metabolites. But in the meantime, Iran, despite having a huge variety of species, unfortunately does not play much role in this global market. According to statistics provided by the World Trade Organization (ITC), the total volume of exports of medicinal plants in the world in 2004 was equal to673462 Tons, which in 2013 increased by 3.7 percent to about 722465 tons. Financially, the total value of exports of medicinal plants from around the world has increased from $ 60 billion to more than $ 100 billion, and it is estimated that this amount will reach more than $ 500 billion by 2050. However, according to available statistics , Iran’s share of this market is about 3% and has a value of 440 billion dollars. However, according to the president of the Union of Exporters of Medicinal Plants, this amount is decreasing every year, and the reason for this is the loss of foreign markets. It is very interesting, although in 2014, according to the official reports of the 11th country in the world after China, India, USA, Japan, Germany, Brazil, South Korea, England, France, Italy in the field of research and presentation of scientific articles on medicinal plants And its products, but unfortunately among the major producing and exporting countriesMedicinal plants and their products have no place and have not succeeded in commercializing their products.
But another interesting point in this regard is that out of 422 thousand plant species in the world, there are about 8 thousand species in Iran.
1728 species are grown exclusively in Iran. According to the official statistics of the Ministry of Jihad for Agriculture, the area under cultivation of medicinal plants was 156,339 hectares and their total production was 173,605 tons. It is estimated that about 3,500 tons of forest and rangeland products are among the medicinal plants and are produced in the wild and annually in Iran. As a result, and according to the available evidence, with proper and practical management, a more appropriate step can be taken to increase Iran’s share in the production of medicinal plants and increase exports.

Conclusion:

Secondary metabolites are valuable compounds that plants have acquired over the years through natural selection, reacting to environmental conditions. Although these compounds do not play a key role in the growth and development of plants like the primary metabolites, but plants always need them to adapt to the environment or reproduce and.. Undoubtedly, medicinal plants have always been one of the rich sources of valuable metabolites. Archaeological and historical studies show that humanity has always attached special importance to these valuable compounds. From ancient lithographs in caves to evidence of the treatment of many diseases in traditional Chinese and ancient Iranian medicine, all show the popularity of these plants. On the other hand, in some historical periods, the value of these plants was so high that they were used in trade and exchange of goods for goods. Iran has a diverse climate, so it is the origin of many medicinal plants, many of which have valuable properties and metabolites. Therefore, the essential need to know the types of secondary metabolites produced in plants, as well as how to study them, is crucial. In fact, in order to have a say in the global market and to have a share of this huge business, we need to pursue this knowledge. In our country, many researchers work in the field of medicinal plants, identifying valuable metabolites in native species, engineering biosynthetic pathways to increase production in plants or capillary roots, which support such a cortex can increase Iran’s position in production and export. Improve herbal medicines. This only requires the discovery of the country’s vast resources, the prevention of the extinction of native species, and ultimately the proper investment of the private and public sectors in this sector.