History of alkaloids Plants with alkaloids content have been used by human even in ancient times for different

reasons for example medicinal, defense, cosmetic, and recreational purposes. The oldest written documents mention the use of alkaloids-containing plants or plant parts and their therapeutic effects. At around 2700 B.C. Chinese Shen Lung explained the medicinal use of traditional Chinese medicine Ma Huang (Ephedra) which contains alkaloid ephedrine. In Papyrus Ebers (1600 B.C. ), the oldest and important medical papyri of the ancient Egypt, over 80 medicinal plants which was described contains alkaloids, for example, opium from Papaver somniferum. In 17th and 18th centuries, plant products were used to treat the symptoms of diseases, like fever (Peruvian bark), pain (opium) and constipation (Ricinus). Opium and henbane had been used to act as anodynes in operation. Extracts of plants containing alkaloids have been widely used as poisons in war and also hunting in the ancient times. The foundation of alkaloids chemistry lies in the 19th century. In year 1804, a German chemist, Friedrich Sertrner discovered morphine. Year 1817 marks the birth of alkaloid, where Sertrner isolated the pure morphine and he described it as the active principle of drug opium. Following his success, others have been stimulated to isolate other alkaloids. At the beginning, the well-established plants were investigated, including Psychotria ipecacuanha, S.nuxvomica, A.belladonna, Cinchona bark, Conium maculatum, to extract emetine, strychnine, atropine, quinine, and coniine respectively. At that time, concerns were regarding the purity, elemental composition and structure of the alkaloid components. However, the structure elucidation of alkaloids were only possible under years of studies after their isolation from plants due to the inadequacy in both physical and chemical methods available in the times. After structure elucidation, the alkaloid is subsequently synthesized. The alkaloid which is synthesized first in the history is coniine in 1886. It was until the 20th century, with emergence of various spectroscopic and chromatographic techniques, over 12 000 alkaloids had been identified by 2008, accelerating the development in alkaloids chemistry. The great biodiversity represents a vast treasure which could benefit to mankind. There are still many more compounds waiting to be discovered and natural product research like those of alkaloids continues to the present day.

Occurrence of alkaloids Alkaloids are produced by various organisms, especially in higher plants, ( e.g., Apocynace, Papaveraceae, Papilanaceae, Solenaceae) . Most of the alkaloids occur in flora, about 1 % in animals and not exceeding 0.5% in fungi and bacteria. Examples of animal alkaloid is Coccinelline 1 from European ladybird beetle and the bufotenin in skin of toads. Alkaloid Psilocybin is found in fungus of genus Psilocybe. Example of bacterial alkaloid is Pyosyanine 2 from Pseudomonas Aeruinosa. Number of plant genera is estimated to be more than 20000, and about 9% of these genera have alkaloids-containing species. The dicotyledones and monocotyledones of the flowering plants (Angiospermae) is the genera with the highest abundancy of alkaloidcontaining plants. In fact, alkaloids are rarely found in Gymnospermae and Pteridophytae. Alkaloids occur inhomogenously over the plant tissues. Several parts of plant which contain alkaloids include roots, stem, bark, leaves, fruits and seed. In some plants (e.g., A.Belladonna ), alkaloids could be isolated from all parts of the plant but for certain plant (e.g.,alkaloid is found only in roots of Aphelandra Squarrosa), only a part of plant have alkaloids. Different tissue in the same plant may not have the same alkaloid content or the ratio of the components of an alkaloid mixture varies for different parts of plants. Based on the type of plant, the maximum concentration of alkaloids is found in the leaves for black henbane, fruits or seeds for Strychnine trees and bark for Cinchona. Alkaloids are present in the form of salt of organic acid (e.g., tartaric acid, acetic acid,malic acid and tannic acid) and a few are with sugar.

Definition and classification: Alkaloids are naturally occurring organic compounds which are nitrogenous bases. An alkaloid is the sub-product of secondary metabolism and could be used by living cells in neurophysiological activity. Alkaloid (alkali) is named so due to its basicity which is attributed to the presence of one or more nitrogen atoms as primary or tertiary amines in alkaloids. Alkaloids therefore can form water-soluble salts in the presence of mineral acids and this property enables the isolation and purification of alkaloid mixture. Some neutral alkaloids and quarternary alkaloids are also found in the nature. Classification of alkaloids is based on the nature of nitrogen-containing structure or the carbon skeleton, such as indole1, piperidine2, pyridine3, pyrrolidine4, isoquinoline5 (e.g. 1 vincristine 2coniine 3 nicotine 4 hygrine 5 ). The origin of nitrogen atom is from the amino acid precursor and usually the carbon skeleton of the amino acid is also retained in the alkaloids with only the carboxylic acid group of precursor is lost via decarboxylation. Therefore, alkaloids could be further subdivided according to the type of amino acid precursor. The principal amino acid precursors usually involve in the alkaloids biosyntheses are lysine, ornithine, nicotinic acid, histidine, tyrosine, anthranilic acid and tryptophan. Building blocks provided trough shikimate, acetate and decarboxylation pathways are also incorporated into the alkaloids structure. The nitrogen atom of a number of alkaloids is acquired trough transamination reactions and incorporate only the nitrogen atom from amino acid and the rest of structure is derived from the various biosynthetic pathways mentioned earlier. These group of alkaloids are usually differentiated with name pseudoalkaloids.

Properties Physical properties of alkaloid are very dependent on their molecular structures. Alkaloids with low molecular weights are colorless liquids, for example, coniine1 and pelletierine2, nicotine3, actinidine4. Alkaloids with higher molecular weights, mostly contain oxygen in molecular structure, are usually colorless crystalline compounds, for example, papaverine. There are also other colored crystalline alkaloids, for example, redviolet cryptolepine. Alkaloids are usually basic due to the lone pair of electron on nitrogen and soluble only in organic solvents like ether, ethanol, chloroform, toluene and insoluble in water whereas alkaloid salts are soluble in water. Water solubility of alkaloids plays an important role for therapeutic purposes. Most isolated alkaloids have optical activity, which is the ability of a compound to rotate a plane-polarized light counterclockwise (levorotatory form) or anticounterclockwise (dextrorotatory form). Compounds containing carbon atom with four different substituents exhibit optical activity. Sometimes, a plant might contain same alkaloids exist as an equimolar mixture of levorotatory and dextrorotatory forms and this mixture is called racemate which is optically inactive. For instances, Vincadifformine which is extracted from different plants have (+), (-) and () forms. Optically active isomers might show different physiological activities.

Therapeutic role of alkaloids The alkaloids have a wide-spectrum and diversity of complex structures which ultimately is credited for their extraordinary broad-range of pharmacological activities in both the human cardiovascular and central nervous system. Even a small quantity of an alkaloid (0.11.0 mg) can bring about a significant pharmacological action on various organs and tissues both of animal and human. However, the potency of an individual alkaloid varies from one another greatly. Alkaloids possess antimicrobial activity out of the many possible biological activities of alkaloids including cytotoxic, antiviral, antiparasitic, anti-inflammatory, antitumerous, antifungal and serotonin realms. Alkaloids are neurotransmitters (Neurotransmitters allow the transmission of signals from one neuron to the next across synapses.) and active agents in nervous system. Many alkaloids either natural ones or modified ones could show euphoric, psychomimetic and hallucinogenic properties in human with some even can induce narcosis, state of unconsciousness and arrested activity. Alkaloids are known as narcotics, stimulants which are active on the human central nervous system, causing disorders and some nonpermanent or permanent changes or behaviours in human central nervous system. In serious cases, it could causes serious impacts like a chronic situation called dependence. These alkaloids are usually opium alkaloids, such as cocaine and thebaine and their derivatives.

Biological role of alkaloids: The roles of alkaloids in plants are mostly undiscovered, and their significance in plant metabolism is still a matter of speculation. A plant species may contain many different alkaloids. Breeding for plants in the absence of alkaloids has shown that alkaloids are not vital. Since majority of alkaloids are very poisonous therefore, can act as chemical defense of plants against attack by microorganisms, insects and herbivores. Moreover, alkaloids have been suggested to function as a reserve form of nitrogen or as protectants against damage by ultraviolet light. Besides, alkaloids are suggested to be waste products or byproducts of various detoxification reactions symbolic a metabolic lock of compounds, which otherwise harmful to the plant.

Alkaloids of genus Alstonia The genus Alstonia is a widespread evergreen trees and shrubs from the dogbane family (Apocynaceae) in major group flowering plants. The name was known as by Robert Brown in 1811, after Charles Alston (16851760), Professor of botany at Edinburgh from 1716-1760. Alstonia, which is also known as devil tree, comprises of about 40-60 species, native to tropical and subtropical Africa, Central America, southeast Asia, Polynesia and Australia, with majority of species in the Malesian region , e.g. Malaysia. These trees can grow very huge. The leaves are leathery, sessile, simple, elliptical, ovate, linear or lanceolate and wedge-shaped at the base. The inflorescence is terminal, and the flowers were found in cymose groups on long stalk. The flowers are small, more or less fragrant and are white, yellow, pink or green, funnel-shaped and with small corolla tube. Each flower has 5 petals and 5 sepals, arranged in four whorls. An example of alstonia spesies shown below is alstonia scholaris

The alstonia plants contain a milky latex, rich in poisonous alkaloids. Alstonia trees are used in traditional medicine. Its latex is used in treating coughs, throat sores and fever. Alstonia trees are widespread and usually not endangered. The alstonia species in study is Alstonia penangiana , which was collected from Penang island in Malaysia. The habitat of this species is terrestrial environment.

1. en.wikipedia.org/wiki/Alkaloid 2. http://www.epharmacognosy.com/2012/07/general-characteristics-of-alkaloids.html 3. http://www.bookrags.com/research/alkaloids-plsc-01/ 4. http://www.epharmacognosy.com/2012/07/function-of-alkaloids-in-plants.html 5. http://books.google.com.my/books?id=a1Z6oJLdgMC&pg=PA206&lpg=PA206&dq=physiological+function+alkaloids&source=bl&ots =Mo9fiWRkHu&sig=bf7EKXzdIy_Tveig_v_3orGs6Cw&hl=en&sa=X&ei=fuguUe2iC8 LSrQffvIGoDw&ved=0CGoQ6AEwCTgK#v=onepage&q=physiological%20function%2 0alkaloids&f=false 6. http://www.scribd.com/doc/24743783/Alkaloid-Its-general-Properties 7. http://www.scribd.com/doc/16523775/Alkaloids 8. medicinal natural product book 9. http://en.wikipedia.org/wiki/Alstonia 10. http://www.payer.de/amarakosa/amara205a.htm http://www.flickr.com/groups/beautifulfloweringtreesoftheworld/pool/tony_rodd/?view=l g