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Biosynthesis of Alkaloids and their
Pharmaceutical importance
Jasmine Juliet .R
Teaching Assistant
Biotechnology Dept
AC&RI, Madurai.
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.
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.
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.
Alkaloids Biosynthesis
• Alkaloids are derived from the products of primary metabolism, with
amino acids, such as:
o Phenylalanine
o Tyrosine
o Tryptophan
o Ornithine
o Lysine serving as their main precursors
• Alkaloids derived from Lysine are widely distributed throughout the plant
kingdom.
Alkaloids Biosynthesis
• Biological precursors of most alkaloids are amino
acids,suchas: ornithine, lysine, phenylalanine, tyrosine, tryptophan, hist
idine, 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.
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
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.
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%
Pathway of Morphine Biosynthesis
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.
Pharmaceutical Effect of Alkaloids
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:
 Naloxone,
 Opioid receptor antagonist, (is a derivative
of thebaine that is present in opium).
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.
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.
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
Psychoactive Alkaloids
Stimulants Hallucinogens Depressants
Cocaine Tropane
Alkaloids
Morphine
Epihedrine Mascaline Codeine
Caffeine Psilocybin Heroin
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.
Antibacterial
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
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.

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Biosynthesis and pharmaceutical applications of alkaloids [autosaved]

  • 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: o Phenylalanine o Tyrosine o Tryptophan o Ornithine o Lysine serving as their main precursors • Alkaloids derived from Lysine are widely distributed throughout the plant kingdom.
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  • 7. Alkaloids Biosynthesis • Biological precursors of most alkaloids are amino acids,suchas: ornithine, lysine, phenylalanine, tyrosine, tryptophan, hist idine, 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.
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  • 9. 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
  • 10. 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.
  • 11. 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%
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  • 14. Pathway of Morphine Biosynthesis
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  • 16. 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.
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  • 19. 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:  Naloxone,  Opioid receptor antagonist, (is a derivative of thebaine that is present in opium).
  • 20. 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.
  • 21. 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.
  • 22. 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
  • 23. Psychoactive Alkaloids Stimulants Hallucinogens Depressants Cocaine Tropane Alkaloids Morphine Epihedrine Mascaline Codeine Caffeine Psilocybin Heroin
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  • 25. 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.
  • 27. 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
  • 28. 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.