Alkaloids , Steroids and their Applications

 

Alkaloids

      Alkaloids are a class of naturally occurring organic compound that mostly contain basic nitrogen atoms. Alkaloids are produced by a large variety of organisms including bacteria, fungi,  plants and animal.      

 

Applications of alkaloids:

• In pharmaceutical:

        Alkaloids are used in the regulation of microbial and schizonticide activity and as pharmaceuticals. Medical use of alkaloids containing plants has a long history and thus, when the first alkaloids were isolated in 19^th century, they immediately found application in clinical practice. Many alkaloids are still used in medicine, usually in the form of salts widely used including  the following.

Alkaloids 

1. Caffeine
2. Physotigmine 
3. Tubocurraine  

There Actions

1. Stimulant, adenosine receptor antagonist.
2. In hibitor of acetylcholinesterase.
3. Muscle relaxant. 

Many synthetic and semisynthetic drugs are structural modification of the alkaloids, which were designed to enhance or change primary effect of drug and reduce unwanted side effects.

• In Industrial:

         Alkaloids can be used as biological fertilizers and control agents in plant protection. Biotechnology opens new possibilities of alkaloids application. The productional achievements are found in the cell and organ cultures. The most well-know application in root cultures are with anabasine, nicotine, harmine and harmaline, hysocyamine, and senecionine. Alkaloids enzymes can be purified from these cultures. Bioreactors and blue white, and fungal biotechnologies are nowadays used in industrial production. 

• In chemistry:

             Some alkaloids are still used in chemistry and modern medicine as natural or modified compounds. Their use is connected to the regulation of Na⁺ ions and channels, mescaric, cholinergic receptors, acetylcholine esterase, opiod and opiate receptors, glycine, 5-HTRs, and others receptors, as well as the regulation of microtubules of the spindle apparatus, antiproliferative activity. Inhibition of some enzymes and induction of apoptosis.

• In agriculture:

                 Prior to the development of a wide range of relatively low-toxic  synthesis pesticides, some alkaloids, such as salts of nicotine and anabasine were used as insecticides their use was limited by their high toxicity to human. Alkaloids are also generally a problem in food; there are some applications in agriculture, especially in plants breeding (alkaloids-rich and alkaloids-poor cultivars). Genetically Modified Organisms (GMOs) can be considered to hold possibilities of vaccine development, especially in plants. Some alkaloids are used as in food receptors as additional components or are consumed as a part of the final product (caffeine, theophylline, piperine, capsaicin).

 

 

Steroids

              Steroids comprise a group cyclical organic compounds whose basis is characteristic arrangement of seventeen carbon atoms in a four-ring structure linked together form three 6-carbon rings and an eight-carbon side chain on carbon 17 (illustration on right).

 

Applications of steroids:

·        Biological significance of steroids:

                 That such diverse physiological functions and effects should be exhibited by steroids, all of which are synthesized by essentially the same central biosynthetic pathway, is a remarkable example of biological economy. Most of these functions, especially those of a hormonal type, involve the transmission of biologically essential information. The specific information content of the steroid resides in the character and arrangement of its substituent groups and in other subtle structural modifications.

1.      Sterols and bile acids:

                        The most generally abundant steroids are sterols, which occur in all tissues of animals, green plants, and fungi such as yeasts. Evidence for the presence of steroids in bacteria and in primitive blue-green algae is conflicting. The major sterols of most tissues are accompanied by traces of their precursors—lanosterol in animals and cycloartenol in plants—and of intermediates between these compounds and their major sterol products. In mammalian skin one precursor of cholesterol, 7-dehydrocholesterol, is converted by solar ultraviolet light to cholecalciferol, vitamin D , which controls calcification of bone by regulating intestinal absorption of calcium. 

The bile acids (cholanoic acids, also called cholanic acids) of higher vertebrates form conjugates with the amino acids taurine and glycine, and the bile alcohols (cholane derivatives) of lower animals form esters with sulfuric acid (sulfates). These conjugates and sulfates enter the intestine as sodium salts and assist in the emulsification and absorption of dietary fat, processes that may be impaired when bile acid secretion is reduced, as in some liver diseases and in obstructive jaundice. The mixture of bile acids found in feces reflects the actions of intestinal microorganisms on the primary bile-acid secretory products (e.g., deoxycholic acid arises by bacterial transformation of cholic acid).

2.      Sex hormones:

                   Steroids that have a phenolic ring A (i.e., those in which ring A is aromatic and bears a hydroxyl group) are ubiquitous products of the ovary of vertebrate animals. These are the estrogens, of which estradiol is the most potent. They maintain the female reproductive tissues in a fully functional condition, promote the estrous state of preparedness for mating, and stimulate development of the mammary glands and of other feminine characteristics. Estrogenic steroids have been isolated from urines of pregnant female mammals of many species, including humans, from placental and adrenal tissues, and, unexpectedly, from the testes and urines of stallions.

3.      Adrenal hormones:

                   The adrenal cortex of vertebrates synthesizes oxygenated progesterone derivatives. These compounds are hormones that are vital to survival and are classified according to their biological activity. The glucocorticoids promote the deposition of glycogen in the liver and the breakdown of body proteins. Mineralocorticoids stimulate retention of sodium in the extracellular body fluids. Cortisol is the principal glucocorticoid in many species, including humans; in most rodents this role is filled by corticosterone.

·        Pharmacological actions of steroids:

                      Aside from their principal physiological effects, all steroid hormones have generalized influences on metabolic systems throughout the body. These are sometimes seen as powerful pharmacological side effects when, either during hormone therapy or through some endocrine abnormality, the body is exposed to excessive amounts of a naturally occurring steroid hormone. In some synthetic analogs of the natural hormones, a desired activity is accentuated, whereas others are minimized. Furthermore, just as naturally occurring steroid hormones of differing biological activity (estrogens, androgens, glucocorticoids, and mineralocorticoids) often act antagonistically, the many steroid analogs include a number of inhibitors of the natural hormones.

·        Biosynthesis of steroids:

                      In plants and animals, steroids appear to be biosynthesized by similar reactions, beginning with acetic acid, assisted by a type of enzyme. The isoprenoid hydrocarbon called squalene, which occurs widely in nature, is thought to be the starting material from which all steroids are made. Enzymatic transformation of squalene produces lanosterol in animals and cycloartenol in plants, which yield cholesterol in both animals and plants. Cholesterol is then converted to bile acids and steroid hormones in animals and to steroids such as alkaloids in plants.

1.      Cholesterol:

                        Steroids are probably synthesized in all vertebrates and in many invertebrates by the same pathway,which includes cholesterol. Biosynthesis of cholesterol is especially vigorous in the liver of vertebrates but also occurs in the intestine, gonads, skin, and immature brain. Cholesterol is barely detectable in the adult brain. The insects, certain mollusks, annelids, and some protozoa do not synthesize cholesterol but must obtain it, or a related sterol, in their

diets. Cholesterol and other steroids are biosynthesized by extension of the enzyme pathway by which terpenoids are synthesized.

2.      Steroid hormones:

                      In vertebrates, cholesterol is the central precursor of all steroid hormones secreted by the testes of the male, the ovaries of the female, and the adrenals of both sexes. These tissues share an embryonic tissue of origin and, in consequence, many enzymes for the transformation of cholesterol. A major (though not exclusive) common pathway involves conversion to progesterone. Progesterone is secreted by the corpus luteum of the ovary, but in the adrenal cortex it is further metabolized to steroid hormones (corticosteroids) such as cortisol and aldosterone.

·        Steroid metabolism in plants:

                               The early steps in the biosynthesis of steroids of both plants and animals are the same, except that in plants lanosterol is replaced by the related compound cycloartenol, which contains a three-membered ring (C9, C10, C19) in lieu of the nuclear double bond of lanosterol. The side chains of the phytosterols, such as stigmasterol, and of the sterol ergosterol of yeasts and other fungi contain extra carbon atoms that are incorporated in reactions involving Sadenosylmethionine, which donates methyl groups in numerous biological processes. Although most plant tissues contain only traces of cholesterol, this sterol is the biogenetic precursor of such important plant steroids as the sapogenins, glycosides, and alkaloids. Because pregnane derivatives are intermediates in some of these transformations, plants and animals appear to have important features of steroid metabolism in common.

• Use of Steroids in Ambulatory Surgery:

                               Postoperative and postdischarge nausea and vomiting (PONV/PDNV) are the most common complications of ambulatory surgery [40]. Gupta et al. [41] in a meta-analysis review, showed the incidence of postoperative Vomiting (0–55%) and postdischarge Vomiting (0–16%). Patients with PONV are significantly more likely to have problems performing activities of daily life have a lower satisfaction score and higher negative economic impact than those not experiencing PONV. Steroids decrease the incidence of PONV, postoperativepain, establish early oral intake, stimulate appetite, and induce a sense of well being (due to increase in release of endorphins). 

Dexamethasone is a corticosteroid with potent anti-inflammatory effects that contribute to decreased wound pain after oral surgery. It also has antiemetic properties in patients receiving highly emetogenic chemotherapy.More recently, dexamethasone has been used as a prophylactic antiemetic in the ambulatory surgery setting. Aesboe et al. conducted a study on use of intramuscular single dose 12 mg betamethasone, 30min before ambulatory hemorrhoidectomy or hallux valgus correction, and they found significantly less PONV, less post operative pain, and better patient satisfaction.

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