The document discusses various enzyme inhibitors including xanthine oxidase inhibitors, cytochrome P450 inhibitors, DHFR inhibitors, and gastric proton pump inhibitors. It provides details on the mechanisms of several specific inhibitors such as allopurinol, ciprofloxacin, trimethoprim, and omeprazole. The document was presented by Sanjay Gopi to Dr. S.D. Joshi of the Department of Pharmaceutical Chemistry at SET's College of Pharmacy in Dharwad, India.
There are many ways that drug-resistant infections can be prevented: immunization, safe food preparation, handwashing, and using antibiotics as directed and only when necessary. In addition, preventing infections also prevents the spread of resistant bacteria.The main cause of antibiotic resistance is antibiotic use. When we use antibiotics, some bacteria die but resistant bacteria can survive and even multiply. The overuse of antibiotics makes resistant bacteria more common. The more we use antibiotics, the more chances bacteria have to become resistant to them.
Introduction
Classification
Therapeutic values of peptidomimetics
Design of peptidomimetics by manipulation of amino acids
Modification of peptide backbone
Chemistry of prostaglandins, leukotrienes and thromboxanes
PEPTIDOMIMETICS , HERE WE HAVE INCLUDED THE INTRODUCTION, CLASSIFICATION, ADVANTAGES , DISADVANTAGES, ITS METHODS PREPARATION, PRINCIPLES OD DRUG DESIGN, ITS CHEMISTRY. STEREOCHEMISTRY, SYNTHESIS AND APPLICATIONS
Active constituent of drugs used in diabetic therapyAkshay Kank
In this slide the active constituents which is isolated from herbal sources used for to treat the type 1 and type 2 diabetes is covered. 'Gymnema' and 'swerita chirata' herbal plant is also covered in the slide.This work help in to focus the herbal emphasis on diabetes.
Analog design is usually defined as the modification of a drug molecule or of any bioactive compound in order to prepare a new molecule showing chemical and biological similarity with the original model compound
Chemistry of Prostaglandins, leukotrienes and thromboxanes(Advance medicinal ...Rohit kaushiK.
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.
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.
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.
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.
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
An informative but short explanation of one of the important PPI pantoprazole. I hope it will help you to make enough sense about pantoprazole. Be connected with me. Thank you .
There are many ways that drug-resistant infections can be prevented: immunization, safe food preparation, handwashing, and using antibiotics as directed and only when necessary. In addition, preventing infections also prevents the spread of resistant bacteria.The main cause of antibiotic resistance is antibiotic use. When we use antibiotics, some bacteria die but resistant bacteria can survive and even multiply. The overuse of antibiotics makes resistant bacteria more common. The more we use antibiotics, the more chances bacteria have to become resistant to them.
Introduction
Classification
Therapeutic values of peptidomimetics
Design of peptidomimetics by manipulation of amino acids
Modification of peptide backbone
Chemistry of prostaglandins, leukotrienes and thromboxanes
PEPTIDOMIMETICS , HERE WE HAVE INCLUDED THE INTRODUCTION, CLASSIFICATION, ADVANTAGES , DISADVANTAGES, ITS METHODS PREPARATION, PRINCIPLES OD DRUG DESIGN, ITS CHEMISTRY. STEREOCHEMISTRY, SYNTHESIS AND APPLICATIONS
Active constituent of drugs used in diabetic therapyAkshay Kank
In this slide the active constituents which is isolated from herbal sources used for to treat the type 1 and type 2 diabetes is covered. 'Gymnema' and 'swerita chirata' herbal plant is also covered in the slide.This work help in to focus the herbal emphasis on diabetes.
Analog design is usually defined as the modification of a drug molecule or of any bioactive compound in order to prepare a new molecule showing chemical and biological similarity with the original model compound
Chemistry of Prostaglandins, leukotrienes and thromboxanes(Advance medicinal ...Rohit kaushiK.
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.
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.
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.
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.
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
An informative but short explanation of one of the important PPI pantoprazole. I hope it will help you to make enough sense about pantoprazole. Be connected with me. Thank you .
Mechanism of drug action (pharmacokinetic and pharmacodynamic )Ravish Yadav
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rational enzyme design
1. DEPT. PHARMACEUTICAL CHEMISTRY
1
Presented to,
Dr. S. D. joshi,
Dept of pharmaceutical CHEMISTRY,
SET’s College of Pharmacy,
Dharwad
From,
Sanjay Gopi
Dept of Pharmaceutical Chemistry
SET’s College of pharmacy
Dharwad.
5. Mechanism :
The active site of XO is composed of a molybdopterin unit with the
molybdenum atom also coordinated by terminal oxygen (oxo), sulfur atoms and a
terminal hydroxide.
In the reaction with xanthine to form uric acid, an oxygen atom is transferred
from molybdenum to xanthine, whereby several intermediates are assumed to be
involved.
The reformation of the active molybdenum center occurs by the addition of
water.
DEPT. PHARMACEUTICAL CHEMISTRY 5
6. During sever liver damage, XO is released into the blood, so blood assy for XO is
a way to determine if liver damage has happned.
Xanthinuria is a rare genetic disorder where the lack of xanthine oxidase leads
to high concentration of xanthine in blood can cause health problems such as
renal failure.
DEPT. PHARMACEUTICAL CHEMISTRY 6
7. XANTHINE OXIDASE INHIBITORS :
Xanthine oxidase inhibitors is any substance that inhibits the activity of xanthine
oxidase.
Xanthine oxidase inhibitors reduces the production of uric acid.
Xanthine inhibitors are of two types
Purine analogues & others
Purine analogues include allopurinol & oxipurinol.
Others include febuxostat & inositols.
DEPT. PHARMACEUTICAL CHEMISTRY 7
9. Mechanism of action of allopurinol
allopurinol is a purine analog, it is a structural isomer of hypoxanthine & is an a
inhibitor of the enzyme xanthine oxidase.
In addition to the blocking uric acid production inhibitor of xanthine oxidase
causes an increase in hypoxanthine & xanthine.
While xanthine can not be converted into purine ribotides, hypoxanthine can be
salvaged to purine ribotides adinosine & guanosine monophosphate.
DEPT. PHARMACEUTICAL CHEMISTRY 9
10. Increased level of these ribotides may causes feed back inhibition of amido
phosphoribosyl transferase – rate limiting enzyme of purine biosynthesis.
Allopurinol therfore decreases uric acid formation may also inhibit the purine
synthesis.
DEPT. PHARMACEUTICAL CHEMISTRY 10
11. CYTOCHROME P450 INHIBITORS
Cytochrome p450 belongs to the super family of protiens containing a heme
cofactor & therefore are hemoprotines.
Many drug interactions are result of inhibition or induction of the CYP450
enzymes.
Enzyme inhibition usually involves competation with another drug for the
enzyme binding site.
DEPT. PHARMACEUTICAL CHEMISTRY 11
13. Mechanism of action
Ciprofloxacin is a broad spectrum antibiotic active against both Gram-
positive & Gram-negative bacteria.
It functions by inhibiting DNA gyrase, a type 2 topoisomerase, &
topoisomerase 4 , enzymes necessary to separate bacterial DNA there by
inhibiting cell division.
DEPT. PHARMACEUTICAL CHEMISTRY 13
14. DHFR Enzyme
DHFR enzyme that reduces dihydrofolic acid to tetradhydrofolic folic acid
using NADPH as electron donor, which can be converted to the kinds of
tetrahydrofolate cofactors.
DEPT. PHARMACEUTICAL CHEMISTRY 14
16. DHFR Inhibitors :
DHFR inhibitor is molecule that inhibits the function of dihydrofolate reductase
& is the type of antifolate.
Examples
Trimthoprim Iclaprim
DEPT. PHARMACEUTICAL CHEMISTRY 16
17. Mechanism of action :
Trimethoprim binds to dihydrofolate reductase & inhibits the reduction of
dihydrofolic acid (DHF) to tetrahydrofolic acid (THF).
THF is an essential precursor in the thymine synthesis pathway & interference
with this pathway inhibits the bacterial DNA synthesis.
DEPT. PHARMACEUTICAL CHEMISTRY 17
18. Trimethoprim’s affinity for bacterial dihydrofolate reductase is several thousand
times greater than its affinity for human dihydrofolate reductase
Sulfamethoxazole inhibits dihydrofolate synthatase an enzyme involved further
upstream in the same pathway
Trimethoprim & sulfamethoxazole is commonly used in combination due to
claimed synergistic effect & reduced development of resistance.
DEPT. PHARMACEUTICAL CHEMISTRY 18
19. GASTRIC ACID SECRETION
Acid secretion is a physiological process of the stomach this acid production is caused by the
highly specialized cell is fundic mucosa, and gastric parietal cells in the stomach.
This gastric acid will directly or indirectly helps the physiological functions like it will initiates
the activation of the enzyme pepsinogen which is involved in digestive process, it will also kills
bacteria and microbes.
20. PROTON PUMP( H+
/ K+
-ATPase ENZYME)
1.Structure :
Present in tubulovesicular and canalicular mestric parital cells
Consist of two subunits a114-kDa-α-subunit (10 trance membrane
helix) and 34-kDa-β-subunit (1 trance membrane helix)
α- subunit-catalytic and transport function
β-subunit- required for endocytic retrieval of H+
/ K+
-ATPase
enzyme from the canalicular membrane
DEPT. PHARMACEUTICAL CHEMISTRY 20
23. GASRTIC PROTON PUMP INHIBITORS :
Proton pump inhibitors (or "PPI"s) are a group of drugs whose main action is
pronounced and long-lasting reduction of gastric acid production. They are the
most potent inhibitors of acid secretion available today.
The group followed and has largely superseded another group of pharmaceuticals
with similar effects, but different mode-of-action, called H2-receptor antagonists.
DEPT. PHARMACEUTICAL CHEMISTRY 23
This class of compound inhibit gastric proton pump in a
non competitive manner by covalent binding of their
active intermediate to the enzyme.
25. Mode of action:-
Physico-chemically PPIs (Omeprazole) represent
a weak base with a pka value of 4.
It can pass through biological membrane as a result
of its lipid permeable properties.
At physiological pH it is unionized & this neutral
form passes freely across biological membrane.
However is an acidic environment with a pH below
4,it is protonated. This result in a limited
permeability. Due to unique structure of parietal cell
with its Secrotory Cannaliculi
DEPT. PHARMACEUTICAL CHEMISTRY 25
26. PPIs (Omeprazole) is trapped with in these
Cannaliculi & undergoes chemical transformation
into activated Pyridinium Sulfenamide (active
enzyme inhibitor).
Which bind covalently to sulphydryl groups of
cysteins of the proton pump (H+
/K+
ATPase)
followed by structural alteration of the enzyme
finally inactivates the catalytic function of the
enzyme.
DEPT. PHARMACEUTICAL CHEMISTRY 26
27. FAQ’S
1)Eplain the process of gastric cid secretion, write an account of developing drug
from lead the inhibition of gastric acid secretion.
2) Discuss mechanism of action of gastric acid secretion & inhibition what are the
drugs used for controlling acid secretion explain their mechanism.
3) Write account on DHFR enzyme inhibitor.
DEPT. PHARMACEUTICAL CHEMISTRY 27
28. REFERENCES
Medicinal chemistry by Burger, 4th
edition Pg.no 103-104
Principles of drug design by Smith Pg.no 17-19
www.google.com
DEPT. PHARMACEUTICAL CHEMISTRY 28