This document provides an overview of a presentation on eicosanoids, prostaglandins, leukotrienes, and thromboxanes. It discusses how these compounds are synthesized from arachidonic acid and their roles in regulating cellular functions and mediating processes like inflammation, smooth muscle contraction, platelet aggregation, and uterine contraction. The presentation covers the biosynthesis, receptors, inhibitors, degradation and biochemical actions of each class of compounds.

1. A Presentation on
Chemistry of Prostaglandins, Leukotrienes and Thromboxanes
Presented by:
Rohit
M.Pharmacy 1st sem
Pharmaceutical Chemistry
220121210016
Presented to:
Dr. Manoj Medal
DEPARTMENT OF PHARMACEUTICAL SCIENECES
GURU JAMBHESHWAR UNIVERSITY OF SCIENCE & TECHNOLOGY
HISAR, HARYANA

2. TABLE OF CONTENTS
EICOSANOIDS
PROSTAGLANDINS
LEUKOTRIENES
THROMBOXANES

3. Eicosanoids are 20-Carbon compounds. They are synthesized in mast
cells and are potent regulators of cellular functions.
Eicosanoids are produced from Arachidonic Acid, a 20-Carbon
polyunsaturated fatty acid (5,8,11,14-eicosatetraenoic acid).
The Eicosanoids are considered as autotcoids.
They act on the cells close to their site of production. Also k/a local
harmone.
They are rapidly degraded.
They are mainly classified in-
Prostaglandins
Leukotrienes
Thromboxanes.
EICOSANOIDS

4. PROSTAGLANDINS
1st discovered in human serum in 1930, were found to be stimulate
uterine contraction and reduce pressure.
Presumed to be synthesized by prostate gland hence the name.
Later found that synthesized in all tissue except erythrocytes.
It have a cyclopentane ring (formed from 8 to 12 carbon atoms) and two
side chains, with carboxyl group on one side.
They differ In their structure due to substituent group double bond on
cyclopentane ring.
Prostaglandins are structurally resemble with prostanoic acid, 20-
carbon fatty acid.

5. Abbreviated as PG, with the class designated by a capital letter
A,B,D,E,F,G,H and I, followed by a number.
PGE and PGF; 1st isolated from the biological fluids.
The letters refer to the different ring structure, except in PGG and PGH:
same ring structure (cyclo endohydroperoxide).
In the same series, depending upon double bonds on the side chains
designated as PGE1, PGE2, PGE3..etc
The number of double bonds varies from 1-3.

6. BIOSYNTHESIS OF PROSTAGLANDINS

9. PROSTAGLANDINS RECEPTORS
They function close to the site of synthesis and are deactivated to
inactive metabolites before moving into the circuation.
Act locally in very low concentration, and acts on GPCR receptors.
INHIBITION OF PROSTAGLANDINS
Corticosteroids (e.g. cortisol) prevent the formation of arachidonic acid
by inhibiting the enzyme phospholipase A2.
Anti inflammatory drugs inhibits the synthesis of prostaglandins.
They block the action of cyclooxygenase.
Aspirin irreversibly inhibits cyclooxygenase.
DEGRADATION OF PROSTAGLANDINS
All eicosanoids are metabolized rapidly.
Degradation mainly occurs in liver and lung.
Two enzymes, namely 15-α-hydroxy PG dehydrogenase & 13-PG
reductase, convert hydroxyl group at C15 to keto group & then to C13 and
C14 dihydroderivative.

10. BIOCHEMICAL ACTION OF PROSTAGLANDINS
The Prostaglandins (PGE, PGA, & PGI2) are vasodilator in nature. So they
decreases blood pressure.
PGE1 & PGE2 induce the symptoms of inflammation (redness, swelling,
edema etc.) due to arteriolar vasodilator, and cause rheumatoid arthritis,
psoriasis etc. so Corticosteroids are used to treat these conditions.
PGE2 & PGF2 are used for the medical termination of pregnancy and
induction of labor.
Pyrogens (fever causing) promote PG synthesis leading to the formation
of PGE2.
Migraine is also due to PGE2.
PGE2 along with histamine and bradykinin causes pain.
PGI2 inhibit platelet aggregation.
They are used in the treatment of gastric ulcers, hyoertention,
thrombosis, asthma etc.
Prostaglandins are also employed in the medical termination of
pregnancy, prevention of conception, induction of labor etc.

11. LEUKOTRIENES
Leukotrienes are synthesized by leucocytes, mast cells, lung, heart,
spleen etc. by lipoxygenase pathway of arachidonic acid.
Leukotrienes are 20- Carbon polyenoic fatty acids having a number of
substituents.
Depending upon the substitutions, they are divided into LTA, LTB, LTD,
and LTE.
Each type is divided into sub-groups depending upon the number of
double bonds which vary from 3-5.
Leukotrienes possess no rings in their strurcture but have three
characteristic conjugated double bonds.

12. BIOSYNTHESIS OF LEUKOTRIENES
HETE- Hydroxyeicosatetraenoic acid, HPETE- hydroperoxeicosatetraenoic acid.

13. LEUKOTRIENES RECEPTORS
Leukotrienes are mainly show their effect by binding with G-Protein
Coupled receptors.
They show their action after binding with this receptors, and produce its
action like inflammation, smooth muscle constriction etc.
LEUKOTRIENES INHIBITORS
Zileuton is a 5-lipoxygenase inhibitor which prevents the formation of
leukotrienes from arachidonic acid.
Leukotrienes antagonists involves Montelukast, Zafrilukast, Pranlukast to
treat allergy and asthma
DEGRADATION OF LEUKOTRIENES
 Biological activity of leukotrienes is terminated by oxidation carried out
by a specific enzyme i.e. cytochrome P450 followed by beta oxidation on
carboxyl group.

14. BIOCHEMICAL ACTION OF LEUKOTRIENES
In general LTs appear to act as mediator in inflammation and anaphylaxis.
Leukotrienes are a hundred times more potent than histamine.
LT-C4, D4 or E4 causes capillary dilation and vascular permeability; they
causes erythema and wheal formtion like histamine.
Action on Bronical Muscles: Inhalation of LTs (C4, D4 or E4) causes
bronchospasm. So these leukotrienes are responsible for constriction of
broncial muscles like in asthma.
LTs- C4 and D4 are potent stimulators of mucus secretion from the
respiratory tract.
So prolonged use of aspirin depresses cyclooxygenase system and PG
synthesis but it did not show its action on lipoxygenase.
Inhibitors of 5-lipoxygenase and leukotrienes receptor antagonists (like
montelulast, zefirlukast) are used in the treatment of allergy and asthma.

15. THROMBOXANES
 Named so because they are identified first in thrombocytes, it helps in
clot formation
Structure is similar to PGs, but have an oxygen atom in the cyclic ring
and contains a six numbered heterocyclic oxane ring.
The most common thromboxane, TXA2, contains an additional oxygen
atom attached both to carbon 9 and carbon 11 of the ring.
TXA2- Vasoconstriction and platelet aggregation thus helping clot
formation. Inhibited by aspirin.

16. BIOSYNTHESIS OF THROMOBXANES

17. Thromboxane
B2

19. ACTION OF THROMOBOXANES
As the concentration of Ca2+ve increases in the cytoplasm it leads to clot
formation and vasoconstiction.
Thromboxanes are vasocontrictor but prostacylins are vasodilator in
nature

20. FUNCTION OF THROMOBOXANES
 Thromboxane is a vasoconstrictor and a potent hypertensive agent, and
it facilitates platelet aggregation.
It is in homeostatic balance in the circulatory system with prostacyclin, a
related compound.
If the cap of a vulnerable plaque erodes or ruptures, as in myocardial
infarction, platelets stick to the damaged lining of the vessel and to each
other within seconds and form a plug. These "Sticky platelets" secrete
several chemicals, including thromboxaneA2 that stimulate
vasoconstriction, reducing blood flow at the site.
INHIBITION OF THROMOBOXANES
 The main drug for thromboxone A2 inhibtion is Aspirin which acts by
blocking COX enzyme.
Thromboxane synthase inhibitors inhibit the final enzyme (thromboxane
synthase) in the synthesis of thromboxane. Drugs e.g. Ifetroban,
Dipyridamole.
The thromboxane receptor antagonists includes terutroban.
Picotamide has activity both as a thromboxane sythase inhibitor and as
a thromboxane receptor antagonist. Ridogrel is another example.