Medicinal Chemistry of Plants - Lab Report Example

Medicinal chemistry of plants The objective of this paper is to identify two organic compounds that are found in plants that have pharmaceutical importance. In connection to this, two organic compounds Acetyldigoxin and Aescin. 1. Acetyldigoxin Is an organic compound which has a systematic name called (3β,5β,12β)-3-{[3-O-Acetyl-2,6-dideoxy-β-D-ribo-hexopyranosyl-(1->4)-2,6-dideoxy-β-D-ribo-hexopyranosyl-(1->4)-2,6-dideoxy-β-D-ribo-hexopyranosyl]oxy}-12,14-dihydroxycard-20(22)-enol ide). It is found in Digitalis lanata, which scientifically is called Grecian foxglove, woolly foxglove (Brauton 45). Figure below shows the chemical structure of acetyldigoxin. The organic compound has cardiotonic action. Cardiotonic drugs increases the levels of the intracellular calcium in the heart muscle. Hence increasing the rate at which the heart contracts thereby leading to more blood being pumped into the body (Graham 19). The plant from which (Digitalis lanata) also known as Woolly Foxglove, belongs to the genus called digitalis. While the family name from which it comes is called Plantaginaceae (Plantain) (Williams 24). Digitalis lanata (Source of acetyl digoxin) Its flowers are elongated and spiked at the top of the plant. They bloom from the lower part of the spike first. Each flower is about 1/3 long and they are creamy white and has brownish veins. They have green sepals which are always white (Brauton 50). The plant generally grows from 0.3 to 0.6 meters in terms of height, or between 13 to 26 inches. The plant prefers to grow in partly shade places which has humus rich soil. In addition, it can also grow in loamy, sandy, and clay soils. However, it can also grow in moist and conditions. Its seeds form in pods that contain small hooks. Therefore these pods are generally transported by human clothes or animal furs. These plants have bitter taste. Their flowers always bloom in the second year. Both its flowers and stems are always woolly and hairy (Graham 48). Botany The plant is generally a biennial plant, however it also grow annually or perennially. This will depend on the species. It is characterized by a cylindrical, thick, downy stem that grows up to a maximum height of 2 m. The leaves which have white hairs below the stem are generally bitter. The plant is native to the British Isles, parts of Africa, and Western Europe. However, it is found today as an ornamental plant throught the world (Brauton 147). Related species which have found use in traditional medicine are include Digitalis grandiflora, Digitalis lutea, also known as (straw foxglove), Digitalis ambigua also called (yellow foxglove), and finally Digitalis ferriginea which also called (rusty foxglove). History The plant was one of the several herbal remedies which was used by the earlier Romans. Even though, its usage as a heart failure medicine can be traced back to the tenth century Europe. The plant was not used not used for treatment up to when a British scientist called William Withering around 1700s. During most period of 1800s the plant was used for treatment of a wide range of disorders and diseases (Graham 23). The first breakthrough came around 1875 when a German chemist isolated pure digitoxin from the plant. In 1875, German chemist Oswald Schmiedeberg first isolated pure digitoxin from digitalis. In 1957, digoxin was first isolated from D. lanata and currently is one of the leading cardiac glycoside which is marketed around the world today (Graham 91). In South States as early as 1820 the drug was being administered in form of powdered leavesand today is acknowledged by all the pharmaceutical companies Digitalis was admitted into the first edition of the Pharmacopeia of the United States (1820) and is currently recognized by all major pharmacopeias. In South America, preparations of the powdered leaves are used to treat asthma, and it is also used as a sedative, and also diuretic. In India however, ointments which have digitalis glycosides are being used to treat burns and wounds (William 61). Chemistry The leaves of the plant low concentrations of active compounds. A variety of wild leaves which have been used for medicinal uses contain Leaves of wild varieties. The leaves that have been used for medicinal purposes have at least 30 different glycosides in total which range between 0.1% to 0.6 %. These are primarily purpurea glycoside A. which yield digitoxin and glycoside B, which is a precursor of gitoxin. During hydrolysis, digitoxin and gitoxin normally lose sugar moieties, releasing their respective digitoxigenin, aglycones, and gitoxigenin. The pathways for biosynthetic synthesis in the production of cardenolides have been known to rely on the enzymes of are reliant on the enzymes of progesterone 5 beta-reductase and malonyltransferase (William 13) Uses and Pharmacology Cardiovascular effects Cardiac glycosides have a positive inotropic effects because it inhibits sodium-potassium adenosine triphosphatase. The enzyme normally leads to accumulation of myocytes thereby resulting in increased cardiac contractility. The drugs also have antiarrhythmic activity, however, at higher dosage it can induce arrhythmias (William 15). 2. Aescin. It is a major active substance in Aesculus hippocastanum (plant) which is a horse chestnut tree. The plant is distributed everywhere because it is highly resistant to environmental conditions. The IUPAC name of Aescin is (2S,3S,4S,5R,6R)-6-{[(3S,4S,4aR,6aR, 6bS,8R,8aR,9R,10R,12aS,14aR,14bR)-9-acetoxy-8-hydroxy-4,8a-bis(hydroxymethyl) -4,6a,6b,11,11, 14b-hexamethyl-10-[2-methyl-1-oxobut-2-enoxy]-1,2,3,4a,5,6,7,8,9,10,12,12a,14,14a-tetradecahydropicen-3-yl]oxy}-4-hydroxy-3,5-bis{[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)-2-tetrahydropyranyl]oxy}-2-tetrahydropyrancarboxylic acid. Figure 2 below shows the chemical structure aescin (Brauton 78). See (Appendix 1) for the detailed structure of Aescin. Applications of Aescin There are three types of pharamaceutical properties which have been attributed to Aescin. These are; anti-inflammatory activities; venotonic properties and anti-oedematous properties Anti-Oedematous Properties Aescin is effective in prevention of oedema in inflammation models that produce has been shown to be effective in preventing the formation of oedema in models of inflammation that reproduce the initial exudative phase, for example, oedema which has been induced by irritative agents (dextran, ovalbumin, cotton pellet, bradykinin and carrageenin), also serous peritonitis which is mainly induced in rats through the injection of formalin and in mice by carrageenan (Graham 40). Anti-inflammatory Aescin is generally used to reduce anti-inflammation by reducing inflammatory granuloma. Venotonic properties Aescin is used to treat patients who have been bitten by poisonous animals for example dogs. Source of Aescin (Chestnut) Its flowers are white in color and they have red and yellow tint at their base. They are 5"-12" long. Its leaves are light green when they unfold and they turn dark green at maturity. They are also upright-oval rounded with their lower branches hanging down. They can grow in most all the soils and maturity they are always 50-75 high and 40’-70 in width (Brauton 143). In summary, Acetyldigoxin Is an organic compound which has a systematic name called (3β,5β,12β)-3-{[3-O-Acetyl-2,6-dideoxy-β-D-ribo-hexopyranosyl-(1->4)-2,6-dideoxy-β-D-ribo-hexopyranosyl-(1->4)-2,6-dideoxy-β-D-ribo-hexopyranosyl]oxy}-12,14-dihydroxycard-20(22)-enol ide). It is found in Digitalis lanata, which scientifically is called Grecian foxglove, woolly foxglove and it is used to treat heart related diseases (Graham 73). While Aescin is a major active substance in Aesculus hippocastanum (plant) which is a horse chestnut tree. The plant is distributed everywhere because it is highly resistant to environmental conditions. Mechanism action of Aescin in chronic venous condition hypoxia of endothelium ATP (12) release of phospholipase A2 prostaglandins release of PAF (12) INFLAMMATORY RESPONSE AESCIN Edema Neutrophil adhesion Neutrophil activation Neutrophil adhesion inhibition (11, 12, 17, 20) Ion channel sensitization; enhanced venous tension/capillary sealing (8, 10) (12) blood flow (12) HYPOXIA (12, 25) (12) Release of elastase & other enzymes Release of fibroblast growth factor (12) Damage to venous walls Vein enlargement (12,25) AESCIN Inhibition of elastase & other enzymes (13, 17) Release of PGF2 (21 Work cited Williams, David. Medicinal chemistry, 7 Ed. New York: LWW. 2012. Print. Graham, Patrick. Introduction to medicinal Chemistry. Chicago: Oxford University Press. 2013. Print. Katzung, Betrum, Susan Masters, Anthony Trevor. Basic and Clinical Pharmacology, 12 Ed. New York: Mc-Graw. 2011. Print. Brauton, Laurence. The Pharmacological Basis of Therapeutics. New York: Mc-Graw. 2010. Print. 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