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.