Biosynthesis and pharmaceutical applications of alkaloids [autosaved]

Alkaloids definition, History of Biosynthesis of alkaloids, Alkaloids application in pharmaceutical field, Biological activity of alkaloids, Alkaloids have different pharmaceutical property their names and their uses in pharmaceutical field.

1. Biosynthesis of Alkaloids and their Pharmaceutical importance Jasmine Juliet .R Teaching Assistant Biotechnology Dept AC&RI, Madurai.

2. Alkaloids - Introduction Alkaloids derived from amino acids and can be synthetized as secondary metabolites by plants and some animals. These compounds play an important role in living organisms. Alkaloids showed strong biological effects on animal and human organisms in very small doses.

3. Alkaloids - Introduction Alkaloids are a huge group of naturally occurring organic compounds which contain nitrogen atom in their structures. These nitrogen atoms cause alkalinity of these compounds. These nitrogen atoms are usually situated in some ring (cyclic) system. For example: indole alkaloids are those that contain nitrogen atom in indole ring system.

4. Alkaloids - Introduction Plant secondary metabolites play multiple roles in the interaction between plants and their environment. Almost 100,000 secondary metabolites have been discovered from plant species. Alkaloids are organic nitrogenous bases, usually in a heterocyclic ring, with characteristic toxicity and marked pharmacological effects in humans and animals.

5. Alkaloids Biosynthesis Alkaloids are derived from the products of primary metabolism, with amino acids , such as: Phenylalanine Tyrosine Tryptophan Ornithine Lysine serving as their main precursors Alkaloids derived from Lysine are widely distributed throughout the plant kingdom. 

6. Alkaloids Biosynthesis Biological precursors of most alkaloids are amino acids,suchas :  ornithine , lysine, phenylalanine,  tyrosine, tryptophan,  histidine , aspartic acid, and  anthranilic acid.  Nicotinic acid can be synthesized from tryptophan or aspartic acid . Ways of alkaloid biosynthesis are too numerous and cannot be easily classified.  However, there are a few typical reactions involved in the biosynthesis of various classes of alkaloids, including synthesis of  Schiff bases  and  Mannich reaction.

7. Synthesis of Schiff base Schiff bases can be obtained by reacting amines with ketones or aldehydes .  These reactions are a common method of producing C=N bonds. In the biosynthesis of alkaloids, such reactions may take place within a molecule, such as in the synthesis of piperidine

8. Mannich reaction An integral component of the Mannich reaction, in addition to an amine and a carbonyl compound , is a  carbanion , which plays the role of the nucleophile in the  nucleophilic addition  to the ion formed by the reaction of the amine and the carbonyl The Mannich reaction can proceed both intermolecularly and intramolecularly .

9. Nicotine Biosynthesis   A tobacco plant, starting from three general-purpose amino acids, ( aspartic acid, ornithine , and methionine ), along with glyceraldehyde , a degradation product of glucose, constructs the pyridine and pyrrolidine portions separately, finally combining them to give nicotine. Nicotine is produced in the roots of the plant and accumulates it in its leaves up to a dry-weight concentration of as much as 9%  

10. Pathway of Morphine Biosynthesis

11. Purpose of Alkaloid Biosynthesis Detailed understanding of alkaloid biosynthesis and mechanisms of action is essential: to improve production of alkaloids of interest , to discover new bioactive molecules , and to sustainably exploit them against targets of interest, such as herbivores, pathogens, cancer cells, or unwanted physiological conditions.

12. Pharmaceutical Effect of Alkaloids

13. In medicine Medical use of alkaloid-containing plants has a long history, and, thus, when the first alkaloids were isolated in the 19th 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: Many synthetic and semisynthetic drugs are structural modifications of the alkaloids, which were designed to enhance or change the primary effect of the drug and reduce unwanted side-effects.  For example:  N aloxone ,   O pioid receptor   antagonist , (is a derivative of  thebaine  that is present in  opium) .

14. Pharmaceutical effects of Alkaloids Among many thousands of modern drugs, about 40% are of natural origin. The widest spectrum of pharmacological action is exhibited by alkaloids, especially, isoquinoline ones. Even in low doses , these alkaloids inhibit the growth of the epithelium carcinoma Hela , epidermic carcinoma KB, and carcinoma P388. anti-cough remedy.

15. Pharmaceutical effects of Alkaloids Berberine , an isoquinoline alkaloid isolated from C. chinensis , inhibits the proliferation and migration of breast cancer ZR-75-30 cells by targeting Ephrin-B2. Berberine also possesses anti-HIV, anti-fungal , cardioprotective , immunoregulative , anti-malarial, anti-inflammatory, antioxidant, cerebro -protective, anti-mutagenic, vaso -relaxing, anxiolytic and analgesic activities.

16. Alkaloid Action Ajmaline antiarrhythmic Emetine antiprotozoal agent , Emesis Ergot alkaloids Vasoconstriction ,  hallucinogenic ,  Uterotonic Morphine analgesic Nicotine stimulant ,  nicotinic acetylcholine receptor agonist Physostigmine inhibitor of  acetylcholinesterase Quinidine antiarrhythmic Quinine antipyretic ,  antimalarial Reserpine antihypertensive Tubocurarine muscle relaxant Vinblastine ,  vincristine antitumor Vincamine vasodilating ,  antihypertensive Yohimbine stimulant ,  aphrodisiac

17. Psychoactive Alkaloids Stimulants Hallucinogens Depressants Cocaine Tropane Alkaloids Morphine Epihedrine Mascaline Codeine Caffeine Psilocybin Heroin

18. Pharmacological effects of Alkaloids - Discussion Alkaloids have high pharmacological and physiological activities: On the CNS they are depressants ( morphine ) or Stimulants (Caffeine). On the autonomic nervous system: Anticholinergics (Atropine , hyoscyamine ). In addition alkaloids include local anasthetics (Cocaine ), agents to treat fibrillation ( Quinidine ) Antitumor agents ( Vinblastine ), Antibacterial ( berberine ) . Atropine is used as antidote in nerve gas poisoning.

19. Antibacterial

20. Alkaloid - Conclusion Several alkaloids have beneficial properties for humans and are used in medicine. For example: Lobeline is used in the treatment of central nervous system disorders and drug abuse and Huperzine A is used in the treatment of Alzheimer’s disease

21. Alkaloids - Highlights Secondary metabolism of plants serves as a rich source for bioactive molecules. Alkaloid biosynthetic pathways are revealing remarkable new enzymatic reactions. Enzymes in alkaloid biosynthesis allow access to a variety of applications in biocatalysis and bioengineering . Alkaloid pathways can be assembled in microorganisms that are tailored to the needs of medicinal chemistry .