maitra enzyme-inhibitor 2002

8/12/2019 Maitra Enzyme-Inhibitor 2002

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January 11, 2003 B.M.S. College of Engineering

Uday Maitra

Department of Organic Chemistry

Indian Institute of Science

Bangalore 560 012

Email: [email protected]

Common enzyme-inhibiting Drugs


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NH2

R

COOH

NH2

NH

NH

NH

NH

NH

O

O

O

OA

B D

E

O

20 common amino acids


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Enzymes have immense catalytic power

(but they cannot alter reaction equilibria)Enzymes are highly specific

The catalytic activities of many enzymes are highly regulated

Enzymes accelerate reactions by stabilizing transition states

For example, 1 molecule of carbonic anhydrase

carries out the following reaction

on 100,000 molecules of CO2per second

CO2 + H2O = HCO3- + H+


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Competitive inhibition

Non-competitive inhibition

V = Vmax [S/(S + Km)]


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Why inhibit enzymes?

Certain disease states may be caused by the product of an

enzyme catalysis

Drugs can target enzymes which are present in pathogens but

not in the host


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NH2 CO2O3P

-

'round-up'

+=

O

OH

O3PO CO

2

CO2

OH

O3PO OH

CO2

O3PO CO2

O

OH

CO2

CO2

OH

O2C CO

2

O

EPSP synthase

glucose

PEP

EPSP

prephenate chorismate

phenylalaninetyrosine

tryptophan

-

-=

-

=+ = -

S-3-P

-

-

- -

The Shikimate Pathway


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[Angiotensin-I]

H2N -Asp -Arg -Val -Tyr -Ile -His -Pro -Phe -His -Leu -CO

2H

Angiotensin- II

Smooth musclecontracton

Aldosterone

secretion

Increasedperipheralresistance

Na -retention

Increasedextracellularfluid volume

Hypertension

A C E

N

CO2H

SH

O

Captopril

NN

O

O COOH

EtO

H

Enalapril

Anti hypertensive agents


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Penicillins and the bacterial cell-wall biosynthesis

D-ala-D-ala

pentaglycine

carbohydrate chain


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OH

NH2

O

N

N

S

O

CO2

-

H

Amoxycillin

N

O OH

OCO

2

-

Clavulanate(beta-lactamase inhibitor)

-Lactamase


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N

NH

O

O

N

NH

O

O

CH3

sugar sugar

Thymidylate synthase

N

N

N

NH

NH2

NH

NH

O

OH

CH

CO2

CH2CH

2CO

2--

N

N

N

NH

NH2

NH

NH

O

OH

CH

CO2

CH2CH2CO2

-

-

N

N NH

NN

NH2

HO

NH

CH CH2CH2CO2

CO2

OH

-

-

-

H

DHF reductase

N5-N10-methylene-THF

dihyrdofolate

tetrahydrofolate

NADPH, H+

H3N COO

OH

+ _

H3N COO+ _

N

NH

O

O

N

NH

O

O

CH3

sugar sugar


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N

N

N

NH

NH2

NH

NH

O

OH

CH

CO2

CH2CH

2CO

2--

-

dihydrofolate

N

N

N

NNH2

NH

NH

O

OH

C

H

CO2

CH2CH

2CO

2--

-

folic acid

N

NNH2

NH2

OMe

OMe

OMe

treimthoprim

DHFR inhibitor

NH2

NH2

NN SO

2

NH2

prontosil

N

N

N

NNH2

N NH

O

NH2 CH

3

CH

CO2

CH2CH

2CO

2--

-

methotrexate

N

O

SO2NNH2H

sulfamethoxazole


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OH

OH H2NHN

CH3

CO2H

CARBIDOPA

OH

NH2

CO2H

tyrosine

OH

OH

NH2

dopamine

OH

OH NH2

CO2H

L-DOPA

DOPA

decarboxylase

DOPAMINE

(blood)

DOPAMINE(brain)

Inhibits blood DOPA decarboxylase

Does NOT cross the blood-brain barrierReduces DOPA intake by 75%

L-DOPA

L-DOPA(brain)

(blood)

DDase

DDase


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NN

NN

OH

OH

OH

H

uric acid

O

NN

NN

OH

O3PO

OH OH

NH2

=

GMP

O

NN

N

N

NHH

O3PO

OH OH

= AMP

NN

NN

OH

H

hypoxanthine

NN

NN

OH

OHH

oxidase

xanthine

xanthine

oxidase

HGPRTase

N

N N

N

OH

H

allopurinol

N

N N

N

OH

OHH

alloxanthine


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CO2H

Arachidonic acid


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O

O

MeSO2

rofecoxib

COOH

O

NO2

NH

S

CH3

OO

N N

F3C

CH3

SO2NH

2

celecoxib

OAc

COOH

COX inhibitors


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Perna Canaliculus

www.lyprinol.com

Principal Ingredients

Natural mono-unsaturated Olive oil 100 mg

Lyprinol GLM pat. lipids (Eicosatetraenoic acid) 50 mg

Vitamin E (D-alpha-Tocepherol) as antioxidant -

0.225 mg.

natural lipoxygenase inhibitor

maitra enzyme-inhibitor 2002

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