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Molecular Docking, Design, Synthesis, in Vitro, in Vivo Antioxidant and

Anti-Inflammatory Evaluations of New Phenylquinoline Derivatives

Conference Paper · March 2016

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Molecular Docking, Design, Synthesis, in Vitro, in Vivo
Antioxidant and Anti-Inflammatory Evaluations of New
Phenylquinoline Derivatives

Manikandan Alagumuthu, Gayathri Jayakrishnan, Hameeda PK and

Sivakumar Arumugam*
School of Bio-Science and Technology, VIT University, Vellore, Tamil Nadu, India.

*Corresponding Author, Email: siva_kumar.a@vit.ac.in Telephone: 0416-2243091 Ext: 2523

Mobile: +91-9047699029 Fax: 0416-2243092

Conference: Avidadham '16, March 18-
19, 2016 @ Anna University, Chennai,
Tamil Nadu, India.
Objectives
 Based on the wide pharmaceutical applications of heterocyclic
compounds, our main objective is to synthesize some
quinolines derivatives that are having good pharmacological
activities like antioxidant and anti-inflammatory.

 Comparing the activity with commercially available drugs by

means of SAR (Structure Activity Relationship) predictions to
ensure the possibilities of the quinoline derivatives as new
nonsteroidal anti-inflammatory agents/analgesics (NSIAS)
drugs.
Why quinolone?
 Quinoline is a heterocyclic compound which is
slightly soluble in cold water but dissolves readily in
hot water and most organic solvents.
 Quinoline is mainly used as a building block to other
specialty chemicals.
 Approximately 4 tonnes are produced annually
according to a report published in 2005.
 Stage-I

Synthesis of phenylquinoline derivatives

Proposed Scheme
R1 OH
1
CHO Molecular I2,
R2 +
Cu2O
R2
2 CH3NO2, Reflux
NH2 24 h N
+ R1
HO
3
4a-l

Scheme 1. Synthesis of substituted 2-(4-phenylquinolin-2-yl) phenol (4a-4l)

Achieved Structures as targeted drug moieties

4a 4b 4c 4d 4e

4f 4g 4h 4i 4j

4k 4l 4m 4n
 Stage-II
In vitro antioxidant and anti-inflammatory studies
DPPH radical scavenging analysis of antioxidant
activity
 The antioxidant activity was evaluated in terms of
hydrogen donating or radical scavenging ability using the
stable radical DPPH
 Ascorbic acid was used as the standard
 Formula
AA%= 100 - [(A2 – A1) x 100]/A0
 Where A2 = absorbance of the sample, the A1= absorbance
of blank and A0= absorbance of control
Results of in vitro antioxidant activity
Compounds % inhibition IC50 (µl/mg)
4a 93.52 1.56
4b 15.58 104.86
4c 90.22 8.34
4d 87.63 14.98
4e 57.91 46.28
4f 81.81 22.31
4g 95.41 0.82
4h 81.16 4.96
4i 90.92 8.12
4j 67.53 28.45
4k 91.55 12.98
4l 82.46 16.61
4m 88.21 10.86
4n 10.87 134.97
Ascorbic acid 90.24 6.98
Control#
#Distilled Water
No inhibition --
 150
140
% Inhibition and IC50 130
120
110
100
90
80
70
60
50
40
30
20
10
0
4a 4b 4c 4d 4e 4f 4g 4h 4i 4j 4k 4l 4m 4n

% inhibition IC50
In-vitro anti-inflammatory activity
 In-vitro Anti-Inflammatory activity was carried out by Human Red
Blood Cell (HRBC) membrane stabilization method
 Indomethacin as standard
 Formula
% Inhibition of haemolysis = 100 x [(OD1-OD2) /OD1]
 Where OD2 = optical density of sample OD1 = optical density of
control
Results of in vitro anti-inflammatory activity
Compounds % inhibition IC50 (µl/mg)
4a 82.98 12.78
4b 45.24 64.98
4c 70.22 20.34
4d 77.62 18.98
4e 45.98 76.28
4f 80.56 21.31
4g 84.89 14.82
4h 70.16 24.96
4i 89.29 10.12
4j 47.53 28.45
4k 88.55 11.98
4l 72.86 26.61
4m 78.01 22.86
4n 24.9 84.97
Diclofenac sodium 90.24 6.98
Control#
#Distilled Water
No inhibition --
 100
90
% Inhibition and IC50 80
70
60
50
40
30
20
10
0
4a 4b 4c 4d 4e 4f 4g 4h 4i 4j 4k 4l 4m 4n
Axis Title

% inhibition IC50
 Stage-III
Animal Studies
Analgesic Activity Tail-flick method
 The selected animals were divided into six groups.
 Each animals of the groups received one of the following 2%w/v of Gum
acacia (2ml/kg) in normal saline, pentazocine (30mg/kg), Ethyl acetate
extract (100mg/kg and 200mg/kg) and ethanol extract (100mg/kg and
200mg/kg) intraperitoneally.
 Diclofenac sodium (100mg/kg and 200mg/kg) was used as the standard.
 Analgesia was assessed with the tail flick apparatus (Analgesiometer).
Anti-inflammatory Activity Carrageenan induced
hind paw edema
 Paw edema was induced by 0.1ml of 1% carrageenan in physiological
saline into sub plantar tissues of the left hind paw of each rat in each
group.
 Indomethacin(5mg/kg), ethyl acetate extracts (100mg/kg and
200mg/kg) and ethanol extracts (100mg/kg and 200mg/kg) were
administered orally 30 minutes prior to carrageenan administration.
 Paw volume was measured at 1, 2, 3 and 6 hours by the mercury
displacement method using a plethysmograph.

% inhibition = Control (% increase in paw volume in 3rdhour) - Test (%

increase in paw volume in 3rd hour) / Control (% increase in paw volume
in 3rd hour) Χ100
 Stage-IV
In silico drug predictions and SAR (Structure Activity
Relationship) studies
Interaction of 4g with COX-1 (PDB: 1CX2)
4g in the binding pocket of 1CX2
Interaction of 4g with COX-2 (PDB:1PXX)
4g in the binding pocket of 1PXX
Studies in progress…..
 RT-PCR for
Pro-inflammatory molecules and
gene expression
Reaction biology
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