Biosynthesis of and Their Pharmaceutical Importance: Alkaloids

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 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.
• 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
Vasoconstriction, hallucinogenic,
Ergot alkaloids
Uterotonic
Morphine analgesic
stimulant, nicotinic acetylcholine
Nicotine
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 Morphine

Alkaloids
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 of Alkaloids and their

• These compounds play an important role in living organisms.

• Alkaloids showed strong biological effects on animal and

• These nitrogen atoms cause alkalinity of these compounds.

• These nitrogen atoms are usually situated in some ring

• For example: indole alkaloids are those that contain nitrogen

• Almost 100,000 secondary metabolites have been discovered

• Alkaloids are organic nitrogenous bases, usually in a

o Lysine serving as their main precursors

 to discover new bioactive molecules, and

 to sustainably exploit them against targets of interest,

 Opioid receptor antagonist, (is a derivative

• Among many thousands of modern drugs, about 40% are of

• The widest spectrum of pharmacological action is exhibited by

• Even in low doses, these alkaloids inhibit the growth of the

• Berberine, an isoquinoline alkaloid isolated from

Cocaine Tropane Morphine

Epihedrine Mascaline Codeine

Caffeine Psilocybin Heroin

• Lobeline is used in the treatment of central nervous

• Huperzine A is used in the treatment of Alzheimer’s

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