This document provides an overview of prostaglandins, leukotrienes, and thromboxanes. It discusses their introduction, classification, chemical structures, biosynthesis, regulation, mechanisms of action, functions, and applications. Specifically, it notes that prostaglandins are derived from arachidonic acid and have diverse hormone-like effects. Leukotrienes are inflammatory mediators produced from arachidonic acid oxidation. They are involved in inflammation and hypersensitivity reactions. Thromboxanes are involved in blood clotting and are derived from arachidonic acid through the action of thromboxane-A-synthase.

1. CHEMISTRY OF
PROSTAGLANDINS,
LEUKOTRIENES AND
THROMBOXANES
Presenting by,
Mr Purushotham KN
Asst.Professor
Department of
Pharm.Chemistry.
SACCP,B.G.Nagara
2021-2022

2. CONTENTS :-
Eicosanoids
1. Prostaglandins
 Introduction
 Classification
 Chemical structure
 Biosynthesis of Prostaglandin
 Regulation of Prostaglandin
 Mechanism of action
 Theraupeutic uses
2. Leukotrienes
 Introduction
 Biosynthesis of Leukotrienes
 Mechanism of action
 Function of Leukotrienes
3. Thromboxanes
 Introduction
 Biosynthesis of Thromboxanes
 Function of Thromboxanes
 Application

3. Eicosanoids
INTRODUCTION
Eicosanoids are oxidised derivatives of 20-carbon
polyunsaturated fatty acids (PUFAs) formed by the
cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome .
Eicosanoids are Classified as
1. Prostanoids
• Prostaglandins
• Prostacyclins
• Thromboxanes
2. Leukotrienes
• Leukotrienes A4
• Leukotrienes B4
• Leukotrienes C4
• LeukotrienesD4
• Leukotrienes E4

4. 3. Lipoxins
• Lipoxins A4
• Lipoxins B4
All Eicosanoids contain 20 carbon atom
Eicosanoids are considred as Locally acting hormone with wide
range of biochemical Function
And also Arachidonic acid is Precursor of eicosanoids in human
beings.

5. Prostaglandins
Introduction
CH3
O
OH
1
2
3
4
5
6
7
8
9
10
11 12
13
14
15
16
17
18
19
20
Prostanoic acid

6.  The prostaglandins (PG) are a group
of physiologically active lipid compounds
called eicosanoids having diverse hormone-like effects in
animals. Prostaglandins have been found in almost every tissue in
humans and other animals. They are derived enzymatically from
the fatty acid that is arachidonic acid
 Prostaglandin are derivative from hypothetical 20 carbon fatty
acid which is called as prostanoic acid and hence the name is
prostanoid.

7. The prostanoid has a 5 carbon cyclopentane ring which is form by
carbon 8 to carbon 12 and it has 2 side chain 1 chain of 7 carbons
these lied above plane of ring and other chain has below the ring.
Each of the biological active prostaglandin it has a hydroxyl
group at carbon number 15.

8. Classification of Prostaglandins
 There is 9 classes of Prostaglandins that are
 Prostaglandin A, Prostaglandin B, Prostaglandin C, Prostaglandin
D, Prostaglandin E, Prostaglandin F, Prostaglandin G,
Prostaglandin H, Prostaglandin I
 Prostaglandin are classified into three series.
 1 series which consist 1 double bond from linoleic acid
Prostaglandin E1.
 2 series which consist 2 double bond from Arachidonic acid
Prostaglandin E2.
 3 series which consist 3 double bond from Eicosapentaenoic acid
Prostaglandin E3.

9. OH
CH3
O
O
H
O OH
Prostaglandin E2
 And double bond between carbon 13 and 14 various
substituent at the cyclopentane ring.
 And also these structure has keto group at carbon 9 and
hydroxyl group at carbon 11.
Chemical structures

10. OH
CH3
O
H
O OH
O
H
Prostaglandin F2
These is the structure of Prostaglandine F2.
It has hydroxyl group at carbon number 9 and 11.
As other biologically active prostaglandin it has hydroxyl
group at carbon number 15.
double bond between 13 and 14.

11. Chemical structure of prostacyclins
Prostacyclins contain additional ring formed by cyclization of
side chain by linkage of carbon 6 to carbon 9 through oxygen
atom on that why it is called as Prostacyclins.

12. O
O
H
O
OH
O
H
CH3

13. Thromboxane had derivatives of oxane ring and it is a six memebered
ring intrepted by oxygen atom. these is interupted by oxygen ring and
also they are synthesized from arachidonic acid.
And also it synthesize in human body and it has additional oxygen
atom joined with carbon 9 and 11.
Prostaglandin are derivative of prostanoic acid which is 20 carbon
fatty acid and they are most potent biologically substances.
It produced in almost tissue except erythrocytes.
Thromboxane

14. Prostaglandin are different from true hormone in human body
Prostaglandins are thought to be local hormone secrete by prostate
hormone.
And also prostaglandin were first isolated from prostate gland
secreation hence it named as prostaglandin.

15. Sweedish scientist Ulf van euler got nobel prize in 1970 for
discovery of prostaglandin.
Prostaglandin actually derived from fatty acid called as Arachidonic
acid which is 20 Carbon fatty acid.

16. Biosynthesis of Prostaglandin
 At cellular level where are the prostaglandins produced and also
prostaglandin are very unstable compound and there half life
around 30 seconds.
 Prostaglandin synthesis is take place from the membrane
phospholipids.
 From the memebrane phospholipid it is cleaved by phospholipid
A2 It release precurser for prostaglandin synthesis which is
arachidonic acid.
 From that arachidonic acid in sequential enzymatic step
prostaglandin would be produced.

17.  This crucial step whenever it is required synthesize phospholipid
A2 releases arachidonic acid from membrane phospholipid there
by prostaglandin synthesis takes place.
 Now key enzyme for prostaglandin synthesis pathway is
Prostaglandin H synthase.
 Prostaglandin H synthase has 2 kind of activity one
cyclooxygenase activity and peroxidase activity.
 Cyclooxygenase activity forms prostaglandin G2 from
arachidonic acid.
 And also peroxidase activity that reduces prostaglandin G2 to
prostaglandin H2.

20. Regulation of Prostaglandin production
 The prostaglandin the key raw material of prostaglandin
production is arachidonic acid derived from cell membrane.
 And it is triggered by a enzyme which is phospholipase A2.
 Now modulating phospholipase A2 activity the prostaglandin
production from arachidonic acid derived from cell membrane.
 And it is triggered by a enzyme which is phospholipase A2
activity the prostaglandin production can be regulated.
 It turns out epinephrine Thrombin, Angiotensin ll , Bradykinin,
vasopressin are positively regulate phospholiphase A2 and that
leads to production of prostaglandin.

21.  Steroid kind of inhibit prostaglandin A2 activity and there by
prevent production of prostaglandin.
 Prostaglandin H synthase its activity triggered by cathecolamines.
 Where as it inhibit by compound like methyl salysilate and similar
compound like aspirin and others.

23. Mechanism of Action
 Prostaglandin found to be working G protein couple receptor
signalling pathway.
 An often prostaglandin stimulation leads to increase in cyclic
Amp and protein kinase.
 A activation followed by several nuclear changes in terms of
chin expression.
 Several Prostaglandin has several effect on different level
example prostaglandin I2 leads to vascular dilation.

24.  Whereas thromboxanes which is secreated or prevently present in
thrombocyte they induce vasoconstriction.
 And also these two has opposite function.
 Now prostaglandin I2 which is known as prostacyclin prevent
platelet aggregation.
 Where as thromboxanes promote platelet aggregation.
 In which prostaglandin F2 are stimulates uterine muscle
contraction sometimes used to terminate pregnancy.
 Now Prostaglandin E and Prostaglandin F has opposing role in
terms of broncho constriction and broncho dilation.

25.  Prostaglandin F leads bronchial smooth muscle constriction
where PGE leads to dilation of the bronchials.
 Prostaglandin E2 and Prostaglandin D2 increase capillary
permeability enabling neutrophill and other imune cell to be
extravated from particular blood capillary near by the tissue and
it also implicate in terms of inflamation.
So that Prostaglandin E2 and prostaglandin D2 are involved in
inflammatory responses.
Now overall prostaglandin prevent are decrease gastric
secreation and increase intestinal mobility.

26. THERAUPEUTIC USES
Abortion : PGs have a place in midterm abortion, missed
abortion. Methotrexate alongwith misoprostol is also highly
successful for inducing abortion in the first few weeks of
pregnancy. Pretreatment with mifepristone improves the efficacy
of PGE2 as abortifacient.
Cervical priming : Applied Intravaginally or in the cervical
canal, low doses of PGE2 which do not affect uterine motility,
make the cervix soft and compliant.

27. Glaucoma : Topical PGF2a analogues like lanatoprost, bimatoprost
that are receptor agonists are the first choice drugs in wide angle
glaucoma.
Peptic ulcer : PGEI (misoprostol) is occasionally used for healing
peptic ulcer.
Avoid Platelet damage : PGI2 (Epoprostenol) can be used to
prevent platelet aggregation and damage during haemodialysis.

28. Leukotrienes
INTRODUCTION
 Leukotrienes is kind of similar leukocytes. It kind of
associated with Leukocytes.
 Trienes are tell us some features of chemical.
 There are 3 consecutive double bond.
 Now we understand leukotrienes as kind of chemical
molecules which might have chemical features 3
consecutive double bond found in leukocytes.
 So these leukotrienes are actually a family of eicosanoids
(arachidonic acid derivatives).

29.  Leukotrienes are inflammatory mediators just like other
arachidonic derivative such as prostaglandin.
 Leukotrienes are a family of eicosanoid inflammatory
mediators produced in leukocytes by the oxidation of arachidonic
acid (AA) and the essential fatty acid eicosapentaenoic acid (EPA)
by the enzyme arachidonate 5-lipoxygenase.
 Leukotrienes use lipid signaling to convey information to either the
cell producing them (autocrine signaling) or neighboring cells
(paracrine signaling) in order to regulate immune responses.
 The production of leukotrienes is usually accompanied by the
production of histamine and prostaglandins, which also act as
inflammatory mediators.

31. 5-lip-oxygenase act on arachidonic acid to form 5-
hydroperoxyeicosatetraenoic acid .
Acts and associate with 5-lox activating protein.
The 5HPETE later converted into leukotriene A4 also it is unstable
and rapidly hydrolyse by the action of enzyme by leukotriene A4
hydrolase to form leukotriene B4 in neutrophils and monocytes.
The LTB4 is one of the most potent inflammation mediating lipids.
And LTA4 (Leukotriene A4) which forms leukotriene C4 which
incorporate with glutathion and with action of LTC4 synthase it
forms leukotrienes C4.
Biosynthesis of Leukotrienes

32. This forms in mast cells and eosinophills.
Later Leukotriene C4 release glutamate to forms leukotriene D4.
Later leukotriene D4 release glycine it forms leukotriene E4.

35. MECHANISM OF ACTION
 Which is usually accompanied with the production of
prostaglandins and histamines which are inflamattory
mediators from arachidonic acid there could be production of
leukotrienes and also in otherside which form prostaglandin
derivatives which also take part in inflammatory response.
 Leukotrienes receptors are class of G-Protein couple receptor
so generally work by elevation of cyclic Amp in the cell and
leads to several inflammatory cytokinin genes.
 But few leukotrienes receptor also nuclear receptor type.

36.  And these receptor generally found in easinophil, endothelial
cells, mast cells.
 In endothelial cells and also found in smooth muscles cells
important role in smooth muscle contraction and they form
physiological role incase of disease.

37. Function of Leukotrienes
Major role of leukotrienes (specially, leukotrienes D4) is to trigger
contraction in the smooth muscle lining the bronchioles.
Contraction of branchioles is triggered by leukotriene and these is
the key underline feature rhinitis or asthma like diseases.
Leukotrienes contribute to the pathophysiology of asthma,
especially in patients with aspirin. Exacerbated respiratory disease
whose symptoms are
Airflow obstruction, Increased secretion of mucus, Mucosal
accumulation, Broncho constriction, Infiltration of inflammatory
cells in the airway wall.

38. Excess of leukotriene leads to anaphylactic shock.

39. Excess of leukotriene leads to anaphylactic shock
And also leukotrienes inhibitors could be useful for patients with later
stages of alzheimer disease.
And also improve memory loss
And also Leukotrienes classified as
Leukotrienes A4
Leukotrienes B4
Leukotrienes C4
Leukotrienes D4
Leukotrienes E4
Leukotrienes designated as 4 because 4 double bond in their structures
are

40. Leukotrienes are involved in the inflammation and immediate
hypersensitivity reaction.
Leukotriene B4
 Increased chemotaxis of polymorphonuclear leukocytes.
 Chemotaxis are directed migration of cell in response to
chemical stimulus such as growth factor.
 Release of lysosomal enzymes, adesion of white blood cells.

41. Leukotriene C4 , Leukotriene D4, Leukotriene E4
• Involved in contraction of smooth muscle.
• They cause Bronchoconstriction, and Vasoconstriction.
• They also called as slow reacting substance of anaphylaxis.
• Anaphylaxis is seveir potentially life threatening allergic reaction.
• And this reaction occur within seconds or minutes of exposure to
allergens.

42. Thromboxanes
INTRODUCTION
 Thromboxane is named for its role in clot formation.
 Thromboxane is a member of the family of lipids known as
eicosanoids and also it is derived from arachidonic acid.
 Arachidonic acid get converted into thromboxane A2 and
thromboxane B2.
 Key enzyme help in these process is known as
thromboxane-A-synthase.
 Both thromboxanes are characterized as 6-membered ether
containing cyclic ring.

44. Biosynthesis of Thromboxanes
o Thromboxanes is synthesized in platelet.
o On the platelet membrane they would be phospholiphase and these
would generate arachidonic acid.
o The arachidonic acid converted initially prostaglandin H2 with the
help of cyclo oxygenase.
o Later prostaglandin H2 is converted into either prostacyclin with the
help of prostacyclin synthase or it can converted into thromboxane
A2 with the help of Thromboxane A synthase.
o These Thromboxane A Synthase enzyme exclusively present in the
platelet membrane. Platelet is the site of thromboxane production.

45. Thromboxane once generated can bind to thromboxane receptor
present in wide variety of cell for example blood vessel.
Thromboxane ultimately leads to G-protein mediating signalling
which elevates calcium level in cytoplasm.
Once calcium level elevated it helps in clot formation or
eventually in vasoconstriction.

47. Function of Thromboxanes
 One of the major function of the thromboxane is to perform
vasoconstriction.
 Thromboxane and prostacyclin has opposite role.
 Prostacyclin has vasodilatory role where as thromboxanes has
vasoconstriction role.
 And also vasoconstriction caused by thromboxanes play a role in
prinz metal ’s angina and blocked coronary artery.
 Any kind of cardiac inflammatory disease one of the leading role
could be played by thromboxanes.
 In immune diet if human body has sufficient omega 3 fatty acid
thromboxane A3 has generated instead of thromboxane A2.

48.  While thromboxane A2 is potent vasoconstrictor and thromboxane
A3 is less potent vasoconstrictor.
 Vasoconstriction mediated effect is less if diet contain omega 3
fatty acid
 In this synthesis of thromboxane by blocking cycloxygenase
specific substance such has aspirin can block production of
thromboxane.
 Other than thromboxane synthase inhibitor inhibit thromboxane
A-synthase.

49. APPLICATION OF THROMBOXANES
 Thromboxanes exert hormone-like Application.
 They interact with G-protein-linked receptors on the cell surface
to activate signal transduction pathways inside the cell.
 TXs modify inflammatory responses but are most well-known for
their role in platelet aggregation, vasoconstriction, and smooth
muscle proliferation – they are an essential part of the wound
repair mechanism.
 Thromboxane synthesis and thus platelet aggregation is inhibited
by non-steroidal anti-inflammatory drugs like aspirin.

51. References
 https://pubmed.ncbi.nlm.nih.gov/32808658/#:~:text=Eicosanoids%20
are%20oxidised%20derivatives%20of,usual%20substrate%20for%20
eicosanoid%20synthesis.
 Medical pharmacology by KD Tripathi, 8th edition Page no-197 to
208.
 Medicinal chemistry by Prof. Surendra Nath Pandeya Page no- 239 to
249.
 https://en.m.wikipedia.org/wiki/Thromboxane#:~:text=Thromboxane
%20is%20a%20vasoconstrictor%20and,from%20platelets%20is%20s
till%20unclear.
 https://en.m.wikipedia.org/wiki/Prostaglandin
 https://en.m.wikipedia.org/wiki/Leukotriene
 Medicinal chemistry by K.Ilango & P valentina Page no-968-999.