Synthesis, Characterization and Evaluation of

New Isatin derevatives for Anti-inflammatory

activity

PRESENTED BY
UNDER THE GUIDANCE OF M.Chaitanya
Dr. K. Swathi (2017MPH40031)
( M. Pharmacy, Ph.D, PDF) Pharmaceutical chemistry
M .Pharmacy 2nd year
 CONTENTS
Introduction
Review of literature
Aim and Objectives
Plan of work
Scheme
Work done so far
Work to be done
References
 INTRODUCTION
 Isatin or 1H-indole-2, 3-dione, is an indole derevative
containing keto group at position 2 and 3 of the ring. This
ring consists of pyrrole ring fused with benzene ring.
 Isatin was first discovered by Erdmann and Laurent in
1841, independently as a product from oxidation of indigo
by nitric and chromic acids. In nature, isatin is found in
many plants, such as Isatis tinctoria, Calanthe discolor
and in couroupita guianensis.
O

O
N
H
1H-indole-2,3-dione
 Isatin is an important class of heterocyclic compounds and
is an indole derevative. These heterocyclic compounds
analogues and their derevatives have attracted strong
interest in medicinal chemistry due to their biological and
pharmacological properties.
 Isatin was a versatile lead molecule for potential bioactive
agents and it’s derivatives were reported to possess wide
variety of important biological activities like antibacterial,
antifungal, anticonvulsant, anti HIV, antituberculosis,
antiviral, anti-inflammatory and antidepressant activity
etc.,
 In present study isatins are important for anti-inflammatory
activity.
 Inflammation is a universal host defence process involving a
complex network of cell-cell, cell-mediator and tissue
interraction, where the redness, swollen, often painful occurs.
 Carrageenan induced rat paw edema model is the screening
method for the in vivo anti-inflammatory activity.
 REVIEW OF LITERATURE
Author Article Published journal Findings
and year
Ravi Jarapula Synthesis, In Vivo Anti- International Compounds with
et.al Inflammatory, and Molecular Jounal of R1=5Cl, 5Br R2=H
Docking studies of New Medicinal Showed good anti-
Isatin Derivatives Chemistry, 2016 inflammatory
O
OH

N NH
activity.
O
N

R2

B. Durga Synthesis, Characterization International Compounds with

Prasad et.al and Anti-Inflammatory Journal of R=Br, CH3, OCH3,
activity of Isatin Derevatives Biological & NH2 were concluded
Pharmaceutical as good anti-
N SO 2NH2 Research, 2012 inflammatory
R
activity.
O
N

H2C N
Author Article Published Journal Findings
and year
Chinnasamy Synthesis, Analgesic, Anti- Indian Journal of Compounds with
Rajaran inflammatory and in-vitro Pharmacy & R=4-CH3, 4-Cl at
Prakash et.al antimicrobial studies of Pharmaceutical para position
some novel schiff and Sciences, 2014. showing better
mannich base of 5- activity
substituted isatin
derevatives.
N R
F N
S N
O
N
CH3
N
CH3

K.Swathi Synthesis and Screening of Internationl Compounds with

et.al Anti-inflammatory activity Journal of R=CH3, C2H5
of Indole Derivatives Pharmaceutical significantly reduce
Research and the inflammation
Biomedical
analysis, 2012.
Author Article Published Journal Findings
and year
K. Swathi et.al Development of Novel Indole Springer Compounds with
Molecules for the Screening International R=CH3, C2H5 showed
of Anti-Inflammatory activity Publishing , 2017 more promising
R O
activity
N (CH2)nCH2 O
R R1
O
N
H

Musab Synthesis, Anti-inflammatory International Compounds with

Mohamed Activity, and in Silico Study Journal of R1=Br, R2=H shows
Ibrahim et.al of Novel Diclofenac and Medicinal maximum in vivo
Isatin Conjugates Chemistry, 2018 activity and scored
Cl
the best binding
energy and virtual
NH

O
Cl screening docking
NH
scores for anti-
1 N
R
inflammatory
O
N
activity.
2
R
 Author Article Published Journal Findings
and year
Blessy Synthesis and evaluation of new An International Compounds with
Priyanka.K Indole derivatives for Journal, 2013 R=H, 5-COOH
et.al antimicrobial and anti- shows good anti-
inflammatory activities inflammatory
N activity.
NH CONH N R
S N
H O N
H

Pramod K. Syntheis and anti-inflammatory Journal of Enzyme Compound 19

Sharma et.al activity evaluation of novel Inhibition and inhibit the ICAM-
tridazolyl-isatin hybrids Medicinal 1 expression by
Chemistry, 2016 89%at an IC50
''
value of 20µM.
O/N-R
X

O
N

(CH2)n

R N
X=H,Br R''=OH, n=2,3 R=Br N
N
 Aim and Objectives
Aim:
To synthesise and characterize the various isatin derivatives
and to perform anti-inflammatory activity
Objectives:
 To synthesise various new isatin derevatives and to perform
anti-inflammatory activity of those compounds.
 To purify the intermediate and final compounds by appropriate
recrystallization and chromatographic techniques.
 To characterize all the new compounds by analytical and
spectral methods like IR, 1H-NMR, Mass spectroscopy.
 Finally, to evaluate anti-inflammatory activity of the
compounds.
 Plan of work
 Synthesis of new isatin derivatives from various substituted
isatins.
 Purification and charcterization of compounds.
 Evaluation of anti-inflammatory activity.
 In vivo studies
 Anti-inflammatory studies
Carrageenan induced rat paw edema model
 In vitro studies
 Antioxidant activity
 DPPH assay
 Nitric oxide (NO) scavenging assay
 Scheme
R O
R N NH 2
reflux
O + NH 2NH 2
N -H2O O
H Hydrazine N
H
Substituted Isatin 5-substituted isatin-3-hydrazone
+
CH3 H3C
R N N CH N N CHO
-H2O H3C
CH3
N O
P-Dimethyl amino benzaldehyde
H
Isatin derevative

R= 7-Cl, 5-Br, 5-F, CH3, 5-I

 SYNTHESIS OF NEW ISATIN DEREVATIVES:
Substituted isatin and Hydrazine Hydrate under
reflux for 1 hr
-H2O reflux

again add a P-Dimethyl amino benzaldehyde for the

intermediate compound

-H2O reflux
After reflux the compound is going to filtrate
dried

New isatin derevatives

 Methods used for the screening of new isatin derevatives
for anti-inflammatory activity
 Carrageenan induced rat paw edema model
Animals required
 Species :Albino Wistar rats
 Weight :200-250g
 Gender : Male
 Number to be used : Wistar rats- 42
 Number of days each animal will be housed : 1 month
 Route : Intraperitonial
Acute toxicity studies:
Acute toxicity studies will be performed as per OECD
guidelines 425.
 Study Design
S.No In each group
Group n=6 Treatment No of animals Purpose

I Normal Vehicle 6 To compare test drug with

(Control) control
II Standard Indomethacin 6 To compare test drug with
standard
III Test Synthesised 6 To assess anti-inflammatory
compound I compound 1 activity
IV Test Synthesised 6 To assess anti-inflammatory
compound II compound 2 activity
V Test Synthesised 6 To assess anti-inflammatory
compound III compound 3 activity
VI Test Synthesised 6 To assess anti-inflammatory
compound IV compound 4 activity
VII Test Synthesised 6 To assess anti-inflammatory
compound V compound 5 activity
Total no of animals 42
 Work done so far
 I did survey on the review of literature for various
substituted isatin derivatives.
 Gathering of chemicals which are economic efficient and
to produce more yield of new products.
 Compared all articles for good and efficient procedure for
my various substituted isatin derivatives.
 Synthesised some of substituted isatins with PDAB.
 Work to be done
 Synthesis and purification of new isatin derivatives.
 Characterization of synthesized compounds by spectrometric
methods such as IR, NMR and Mass Spectroscopy.
 In vivo anti-inflammatory activity studies
 Carrageenan induced rat paw edema model
 In vitro antioxidant activity studies
 DPPH assay
 Nitric oxide (NO) scavenging assay
 In-Silico studies
 References
 Prakash, C., S. Raja, G. Saravanan. “Synthesis, Analgesic,
Anti-inflammatory and In Vitro Antimicrobial studies of some
Novel Schiff and Mannich Base of 5-substituted Isatin
Derivatives”. International Journal of Pharmacy and
Pharmaceutical Sciences, Vol. 6, 160-6, 2014.
 Ravi. J, Kiran. G, Sarangapani. M and Sriram. R, “Synthesis,
in Vivo Anti-Inflammatory Activity, and Molecular Docking
Studies of New Isatin Derivatives”, International Journal of
Medicinal Chemistry, 2016.
 K. Swathi and M.Sarangapani, “Synthesis and Anti-
Inflammatory Activity of a Novel series of Isatin Hydrazone &
Isatin Thiosemicarbazone Derivatives”, World Journal of
Pharmacy And Pharmaceutical Sciences, Vol 3, 2070-78, 2013.
 Sarrah Sattar. J, Mustafa .N, Ammar A.F, “Evaluation of Anti-
Inflammatory Activities of Newly Synthesised Isatin
Derivatives In Rats”, International Research Jounal of
Pharmacy, Vol 10, 2019.
 Musab Mohamed. I, Tilal. E, Mosab Y, “Synthesis, Anti-
Inflammatory Activity, and In-silico study of Novel Diclofenac
and Isatin Conjugates”, International Journal of Medicinal
Chemistry, 2018.
 Subhas .S, C.B.Mahendra kumar and C.Mallikarjuna,
“Synthesis, Anti-Inflammatory and Antibacterial activities of
some substituted Isatin and Isatin fused with 3-Substituted 4-
Amino-5-Mercapto-1,2,4-Triazoles”, International Journal of
Chemical Science, Vol 13, 2015.
 Tarek B. Ahmad, David. R, Joshua. S, Michael. K, Peter. M,
Lisa M.S, Lei Liu and Kirsten. B, “Anti-Inflammatory Activity
and Structure-Activity Relationships of Brominated Indoles
from a Marine Mollusc”, Marine Drugs 2017.
 Aldo A, Silvia B, Massimiliano G, Alberto L, Alessandra L, Rita
M, Mirella R, Lucilla V, Mauro Andrea C, Giuseppe P, Rinaldo
C, Emanuela G, “New isatin derivatives with antioxidant
activity”, European Journal of Medicinal Chemistry, Vol 45,
2010.