SYNTHESIS AND BIOLOGICAL EVALUATION OF NOVEL

NITRIC OXIDE (NO) DONATING COMPOUNDS

Under the guidence of
Dr.V.V.S Rajendra prasad,PhD.
Department of pharmaceutical chemistry,
Vishnu Institute of pharmaceutical education & Research.
Vishnupur,Narsapur,Medak(D).
By
A.Anil Kumar
K.Parameshwar
N.Bharath
N.Vinay

INTRODUCTION NITRIC OXIDE

Nitric oxide was first identified as a gas by Joseph Priestly in 1772.

Molecule consisting of just one atom of oxygen and one atom of nitrogen.
It is biosynthesised by L-arginine, oxygen & NADPH.
Lipid soluble & Easily cross the cell membrane.
Short lived, usually degraded or reacted within a few seconds

Role of Nitric oxide in human physiology

Nitric oxide (NO) is an endogenous messenger molecule that is extensively
involved in the physiologic regulation of different tissues in the human body.
It plays a important role in
1.Nervous System
2.Circulatory System
3.Muscular System
4.Immune System
5.Digestive System
In human body it acts as a
1. Neurotransmitter
2. Vasodilator
3. Bactericidal agent
4. Inhibition of smooth muscle contraction

 NO regulates apoptosis in wide range of cell types, although

its precise effects are dependent on the amount of NO used
and the type of cell. It has been shown to both induce and
inhibit apoptosis. Nitric oxide has been demonstrated to
inhibit apoptosis in a number of cell types including
leukocytes, hepatocytes, trophoblasts and endothelial cells.

INTRODUCTION TO ACRIDONES

Grabe and caro discovered acridone in a high boiling fraction of coal tar.
Acridones are the oxidized products of acridines.
Acridines have provided an important series of chemotherapeutic drugs.
These compounds are well known for their high toxic activity ,how ever
their clinical application is limited because of side effects.

 Acridones are mostly used in anti bacterial and anti

fungal activities.
These play key role in antiparasitic and as
anticonvulsants.
Acridones are bio-carrier to target the selective cells
in the human body.

SYNTHESIS OF ACRIDONE DERIVATIVES

The methods of preparation of acridone or substituted
acridones consist of the following:
1.Synthesis of diphenylamine-2-carboxylic acids
by ulmann reaction
2.Cyclization of diphenylamine-2-carboxylic acids
to form acridones
Ulmann reaction:
The Ullmann reaction consist essentially of the interaction of
a halogen substituted benzene with aniline to give a diphenyl
amine, a carboxylic group being in the ortho position to either
the halogen or to the amino group

COOH

COOH

COOH

COOH

+
Cl

H2N

Cl

N
H

Cu

Cu

COOH
Cu

+ HCl +
N
H

COOH

Cyclization of diphenylamine-2-carboxylic acids

More recently, polyphosphoric acid has been introduced
for the ring-closure of diphenylamine-2-carboxylic acids.
No phosphorylation occurs, and alkoxy groups are less
labile to become hydrolyzed. The diphenylamine-2carboxylic acid is usually treated with 20-60 parts of
polyphosphoric acid for 3 hours at 1000C on a steam bath.
The mixture is then poured into hot water and made
faintly alkaline with liquor ammonia. Yellow precipitate of
acridone was obtained.

O
C OH

OH
H

HO
COOH +
H

COOH

(+)

(+)

O
C

N
H

COOH

ACRIDONE DERIVATIVE SYNTHESIS SCHEME

positions

substutions

H ,COOH

R1

COOH ,H

BIOLOGICAL EVALUATION

CONCLUSION
Designed molecules were synthesized and
characterized, novel derivatives constitute carboxamide
substitution followed by different tertiary and secondary
amine substitutions, all the molecules exhibit in both
protonated and deprotonated forms. Lipophilicity values
were existed raging from 2.17 to 5.24. All the molecules
are not able to inhibit the growth of both of micro
organisms. The cytotoxic activity of these molecules
against various drug sensitive and resistant cancer cell
lines will be studied.

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