Synthesis and evaluation of central antinociceptive activity of ring substituted chalcones; molecular docking studies with monoacylglycerol lipase (MAGL) enzyme

Article abstract of DOI:10.13005/ojc/3404024

Chalcones possess Michael acceptor property due to the presence of α,β-unsaturated enone moiety in their structure. In the present study, molecular docking was performed to predict binding affinity of ring substituted chalcones with Monoacylglycerol lipase (MAGL), a serine hydrolase enzyme which can inhibited by Michael acceptors such as maleimide derivatives. 3, 4-Dimethoxy derivative, 3 h with -44.45 kJmol^-1 of interaction energy, exhibited highest binding affinity and formed Pi-Sulphur interactions with methionine-123 residue of MAGL enzyme. As MAGL is an emerging target for antinociceptive drug development, ring substituted chalcones were synthesized and evaluated for their central antinociceptive activity using tail immersion and hot plate methods. The results revealed that compound 3 h chalcone bearing methoxy groups at 3^rd and 4^th positions of phenyl ring exhibited good antinociceptive activity in both the models. Good correlation was observed between antinociceptive activity and binding affinity toward MAGL in case of compound 3 hour.

Full text of DOI:10.13005/ojc/3404024

ISSN: 0970-020 X
CODEN: OJCHEG
2018, Vol. 34, No.(4):
Pg. 1890-1897
ORIENTAL JOURNAL OF CHEMISTRY
An International Open Free Access, Peer Reviewed Research Journal
www.orientjchem.org
Synthesis and Evaluation of Central Antinociceptive activity of
Ring Substituted Chalcones; Molecular Docking Studies with
Monoacylglycerol Lipase (MAGL) Enzyme
SHAHEEN BEGUM1*, ARIFA BEGUM1 and BHARATHI KOGANTI1.
Institute of Pharmaceutical Technology, Sri Padmavati Mahila Visvavidyalayam
(Women’s University), Tirupati 517502, Andhra Pradesh, India.
*Corresponding author E-mail: shaheen.pharmchem@gmail.com
http://dx.doi.org/10.13005/ojc/3404024
(Received: April 27, 2018; Accepted: June 19, 2018)
ABSTRACT
Chalcones possess Michael acceptor property due to the presence of α,β-unsaturated enone
moiety in their structure. In the present study, molecular docking was performed to predict binding
affinity of ring substituted chalcones with Monoacylglycerol lipase (MAGL), a serine hydrolase
enzyme which can inhibited by Michael acceptors such as maleimide derivatives. 3, 4-Dimethoxy
derivative, 3 h with -44.45 kJmol-1 of interaction energy, exhibited highest binding affinity and formed
Pi-Sulphur interactions with methionine-123 residue of MAGL enzyme.As MAGL is an emerging target
for antinociceptive drug development, ring substituted chalcones were synthesized and evaluated
for their central antinociceptive activity using tail immersion and hot plate methods. The results
revealed that compound 3 h chalcone bearing methoxy groups at 3rd and 4th positions of phenyl ring
exhibited good antinociceptive activity in both the models. Good correlation was observed between
antinociceptive activity and binding affinity toward MAGL in case of compound 3 hour.
Keywords: Ring substituted chalcones, Monoacylglycerol Lipase, Hot plate test,
Tail immersion test, Molecular docking.
INTRODUCTION
role in progress of pain signalling [sodium, potassium
and transient receptor potential (TRP) channels] and
receptors involved in pain perception [imidazoline(I2),
Pain is now recognized as a global
health problem, with an urge for effective and
safer therapeutic agents. Pathophysiology of pain
is complex despite of the recent advancements
that has taken place in the area of molecular and
neurobiology1,2. Current findings suggest variety of
drug targets including ion channels, playing pivotal
adenosine(A1Rs) and cholecystokinin (CCK)]3-5
.
Enzymesoftheendocannabinoidcascade,especially,
fatty acid amide hydrolase (FAAH), α, α, β-Hydrolase
domain containing4,6,12 (ABHD-4, ABHD-6,
ABHD-12)and Monoacylglycerollipase(MAGL) which
can hydrolyze endocannabonoids, 2-arachidonyl
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ethanolamine (AEA) and 2-arachnidonyl glycerol
(2-AG) are among the promising pain targets
and the compounds that alter their respective
endocannabinoid levels have been represented as
potential antinociceptive agents6,7.
chalcones interact with reactive groups of enzymes
such as sulfhydryl functionality present in cysteine
(Fig.1) which results in the loss of enzymatic
activity23-26
.
Chalcones derived from natural origin or
Monoacyl glycerol lipase (MAGL),
terminates pharmacological responses of 2-AG by
hydrolysing it into arachidonic acid, a familiar pro-
inflammatory mediator and glycerol8.2-AG regulates
various neurological and metabolic functions such as
neuropathic pain, anxiety and neuromodulation by
acting as a full agonist for the cannabinoid receptor
type 1 (CB1) receptors9. Hence, MAGL inhibition
is a promising strategy to treat diseases in which
higher 2-AG concentrations would be beneficial,
in particular, pain and neuromodulation. MAGL is
a member of serine hydrolase class of enzymes.
It is highly expressed in brain, particularly at the
presynaptic terminals and in areas of brain where
CB1 receptors are localized10,11.Synthetic drugs such
as rivastigmine, saxagliptin, boceprevir, orlistat and
β-lactam antibiotics are few examples of clinically
Fig.1. Enzyme inhibition results from interaction of
sulfhydrul group and chalcone
synthetic chalcones bearing different substituent
groups such as carboxylic acid or acetamide group or
substituted urea exhibit peripheral as well as central
antinociceptive activity.Mechanism of these potential
molecules is not well defined. Literature indicates
the probable mechanism might involve COX-2 and
iNOS mediated pathways27.
approved inhibitors of human serine hydrolases12,13
.
In our earlier studies, we have performed
molecular docking studies of ring substituted
chalcones on iNOS and COX-2 enzymes and
reported that these molecules have good binding
affinity for both the enzymes, where electronic
effects, hydrogen bonding ability have profound
influence on the binding interactions. Molecular
and pharmacokinetic properties prediction showed
that these chalcones have good brain penetration
permeability28.
Literature survey revealed that MAGL enzyme can
be inhibited by several chemical entities such as
arylthioamides, carbamates, disulphide containing
compounds and maleimides. These inhibitors act
either by acting on catalytic nucleophilic amino
acid Ser-122 (Ser-His-Asp triad) or by forming
Michael adduct with sulfhydryl groups of aminoacids
(Cys-204&Cys-242 present in the active site14-16
.
Chalcones obtained either from natural
sourcesorpreparedsynthetically,inhibitabroadrange
of enzymes, to mention a few, inducible nitric oxide
synthase (iNOS), lipooxygenase (LOX), xanthine
oxidase, tyrosine kinase, monoamine oxidase,
soluble epoxide hydrolase, cyclooxygenase-2
(COX-2), angiotensin converting enzyme (ACE)
and β-secreatase17-22. Diverse set of therapeutic
activities have been ascribed to chalcones such
as antitumoral, anticancer, antioxidant, antifungal,
antimitotic, chemoprotective, anti-inflammatory,
antimicrobial, antinociceptive and antibacterial
In view of the capability of chalcones
to interact with variety of enzymes and with the
assumption that they may bind and form Michael
adduct with cysteinyl groups of MAGL, it was
proposed to dock a series of ring substituted
(different electron releasing or withdrawing groups
on ring B) chalcones with MAGL enzyme. Further,
these chalcones were synthesized and their central
antinociceptive activity was screened using the
tail-immersion and hot-plate tests to find a correlation
between in silico and in vivo studies.
MATERIALS AND METHODS
activities which invigorates interest of medicinal
Molecular Docking studies
chemists. Presence of the, α,β-unsaturated enone
unit in the chalcone is believed to be highly active,
which impart enzyme inhibitory efficiency to this
molecule. Michael-addition reaction occurs when
Molecular docking studies on MAGL
enzyme was carried out on the crystal structure of
MAGL which was retrieved from PDB data bank

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(PDB ID: 3PE6) using CDocker protocol, module of
Discovery Studio Version 3.1 (Accelrys). CDocker
is a more reliable grid-based protocol wherein
CHARMM force fields are applied.While docking the
molecules, 10 Å of grid extension was set around the
active site of enzyme. Hydrogen atoms were added
to the crystal structure of MAGL and all ionisable
residues were set at pH 7. For each chalcone
(Fig. 2), ten best binding poses were generated.
Input site sphere dimensions were set to -11.2454,
19.8898, -8.42488 and 11.7564 respectively and
binding interactions were analysed. The molecular
docking scores were calculated as binding free
energies (kJ/mol).
Sigma-Aldrich, USA chemicals. All other chemicals
are of AR grade.“Thermonik Precision Melting point
cum Boiling point apparatus, Model C-PMB-2 was
used to determine the melting points which were
uncorrected. Formation of the final compounds
was monitored by thin-layer chromatography (TLC).
The infrared (IR) spectra were recorded using KBr
pellets on Perkin-Elmer Spectrum-BX-I Infrared
Spectrophotometer (cm-1). The H NMR spectra
1
were recorded in deutero chloroform (CDCl3) on
Jeol-400MHz instrument. Mass (m/z) spectra were
obtained using LCMS-8030 mass spectrometer.
General procedure for the preparation of ring
substituted chalcones (3a-j)
Chalcones were synthesized according to
the previously described methodology29.Asubstituted
acetophenone (5 mmol) and benzaldehyde
(5 mmol) were dissolved in dry methanol (30 ml).To
this methanolic solution, 5ml of sodium hydroxide
(50%) was slowly added. Stirring was continued
(20 min.-1 h) at room temperature and to neutralize
R1 = H, 4-F, 4CI, 2,5-(CI)2, 4-NO2, 4-OH, 4_OCH3, 3,
4-(OCH3)2, 3, 4, 5-(OCH3)3, 4-CH3
1
the contents, N HCl was added. Reaction time
taken for the completion of reactions is mentioned
in Table.1. A mixture of ethyl alcohol and water was
used for recrystallization. The synthetic procedure
and reaction conditions for chalcones are illustrated
in scheme 1.
Fig. 2. Chalcones selected for molecular docking studies
Chemistry
Substitutedacetophenonesandbenzaldehyde
were purchased from Merck & Co., India and
Scheme 1. Synthesis of chalcones. Reagents and reaction conditions:
(i) 50% NaOH, CH3OH, room temperture
cellulose solution freshly before administration
Pharmacological studies
The protocol used to perform the
to animals. Tramodol was used as the standard
(10mg/kg) drug which was administered orally
to compare the results of the synthesized
compounds.
pharmacological activites was approved by
institutional animal care and use committee ((1677/
PO/a/12/IAEC/44).Male Swiss Albino mice (25-32 g)
were used which were acclimatized to the laboratory
for at least 2 h before testing. The test compounds
were suspended well in 1% sodium carboxymethyl
Hot-Plate Method
This test was performed in order to measure
the latency time (licking the hind- paws/ jumping off

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the hot plate) using hot-plate30. The hot plate used
in this study was set to a temperature of 55 1oC.
The saline solution (0.1 ml/10g, p.o) was given to
control animals whereas test group animals received
synthesized compounds (50 mg/kg, p.o). To reduce
the risk of tissue damage or injury, the cut-off time
for the latency time was set at 20s.
divided into two important regions;Leu-148, Ala-164,
Leu-176, lle-179, lle- 211, Leu-213, Leu-214 and
Val-217 side chains form hydrophobic pocket, while
polar groups of Tyr-58, His-121and His-272 side
chains, Glu- 53, Arg-57 and Ala- 51 form hydrophilic
pocket10-11
.
N-arachidonyl maleimide (NAM), a reported
maleimide derivative (Michael acceptor) with potent
MAGL inhibitory activity was used as standard
inhibitor for comparing the molecular docking results
of the synthesized chalcones. Maleimides acts as
Michael acceptors and interact with cysteine residue
of MAGL enzyme. Molecular docking studies of
NAM with MAGL showed that the long aliphatic
chain of the standard inhibitor was found to be
located in a way that the terminal alkyl part connects
with alkyl portions of Val-191 and Lys-278 via
alkyl-alkyl interactions.The polar heterocyclic pyrrole
ring of NAM showed π-π stacking interactions with
Phe-159 where as the Pi electrons involve in Alkyl-Pi
interactions with Leu-213 and Leu- 214 located near
the active site. The interaction energy obtained for
NAM was -60.98 kJmol-1 indicating its high affinity
towards the enzyme (Figure 3).
Table 1: Reaction time taken for completion
of different reactions
Compound
No.
R
Reaction time
3a
3b-3d
3e
3f
3g-3j
4-H
4-F,4-Cl, 2,5-(Cl)2
4-NO2
>45min.
<30 min.
<20 min.
>50 min
>40 min.
4-OH
4-OCH3, 3,4-
(OCH3)2,3,4,
5-(OCH3)3,
4-CH3
Tail-immersion test
Inthisanimalmodel,afteroraladministration
of the chalcones or saline, mice were covered using
cloth while their tails were immersed in a beaker
of hot water (55
1°C). The latency (sec.), for
the animal to withdraw its tail from hot water was
recorded. As long exposure to hot water may lead to
tissue inflammation, a cut off of 15 sec. was set31.
RESULTS AND DISCUSSION
Chalcones containing different electron
withdrawing and electron releasing substituent
groups on various positions of B ring (3a-j) were
subjected to molecular docking studies. Based
on the results observed in these studies, we have
synthesized the chalcones and screened them for
their potential central antinociceptive activity using
pain models such as tail immersion assay and
hot-plate tests.
Molecular Docking studies
Fig. 3. Binding mode of NAM in the active site
of MAGL enzyme
MAGL enzyme belongs to α/β serine
hydrolase super family and comprise of catalytic
triad, nucleophilic elbow and oxyanion hole as the
main structural elements. Catalytic triad constitutes
the residues Ser-122, Asp-239 and His-269 in the
the binding pocket. The catalytic site of MAGL is
Molecular docking studies of chalcones
within the active site of MAGL revealed one particular
observation with respect to all chalcones is the
formation of S-π interactions (Sulphur-Pi) of both
the phenyl rings of chalcone with crucial amino acid

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residue Met-123 residing adjacent to Ser-122, part
of catalytic triad. Methionine side chains are both
lipophilic, flexible and divalent sulphur behaves as a
weak negatively polarized atom when interacts with
phenyl rings. Ala-126, Ala-127 and Ala-216 were
found to interact and have Pi-alkyl interactions with
the phenyl rings of chalcones. Amide-Pi stacking
interactions were also observed with His-121 and
ring B which holds carbonyl group of α,β-unsaturated
carbonyl system. These interactions were observed
with all the docked chalcones irrespective of their
substituent groups. Obtained results were different
from our assumption that chalcones may bind and
form Michael adduct with cysteinyl groups of MAGL.
the methoxy containing chalcones, 3,4-dimethoxy
chalcone exhibited highest binding affinity with the
enzyme (-44.45 kJ/mol) indicating the importance
of substitution on chalcones. Methoxy hydrogens,
situated at 3rd position of this chalcone found to form
hydrogen bonding with Phe-209.Pi-donor hydrogen
bonds were observed between phenyl rings of
chalcones and backbone nitrogen atoms of amino
acids Ala-126 and Ile-127(Figure 4).
Table 2: Docking scores for substituted chalcones
(3a-j) with MAGL using CDocker (Discovery Studio)
Compound R
No.
Interaction
Energy
Interacting
Amino acids
(kJ mol-1)a
When unsubstituted chalcone was docked
in to the binding site of MAGL, Van der Waals
interactionswereobservedbetweenringAandamino
acid residue Ile-217 (-38.56 kJ/mol.). Introduction of
fluorine increases binding affinity (-40.23 kJ/mol),
fluorine forms a hydrogen bond with Val-217.
Replacement of fluorine with chlorine resulted in
further increase in binding affinity (-40.98 kJ/mol)
indicating that presence of halogens are favourable
for binding with the target protein MAGL.
3a
3b
3c
3d
3e
3f
4-H
-38.56
Met-123
4-F
4-Cl
-40.23 Met-123, Ala1-26 Ala-216
-40.98 Met-123, Ala-126 Ala-216
-39.24 Met-123, Ala-126 Ala-216
-41.43 Met-123, Ala-126 Ala-216
-40.40 Met-123, Ala-126Ala-216
-43.23 Met-123, Ala-126 Ala-216
2,5-(Cl)2
4-NO2
4-OH
3g
3h
3i
4-OCH3
3,4-(OCH3)2 -44.45 Met-123, Ala-126Ala-216
3,4,5-(OCH3)3 -42.24 Met-123, Ala-26Ala-216
3j
4-CH3
-
-37.43 Met-123, Ala-216, Ala126
-60.98 Phe-159,Val-191,Lys-273,
Leu-123, Leu-124
NAM
Introduction of electron withdrawing
group (-NO2) increased the binding affinity for
the enzyme (-41.43 kJ/mol) when compared to
unsubstituted chalcones (-38.56 kJ/mol). Among
a.The score represents the highest ranking poses obtained
from the docking of each compound bound to MAGL
enzyme
The results obtained in the docking studies
with MAGL indicate that synthesized chalcones have
good affinity for this enzyme as they could interact
with one of the important amino acid (Ser-122)
present in the catalytic triad. Results demonstrated
that substitution with either halogens, electron
withdrawing and releasing groups are favourable for
binding with the enzyme.
Chemistry
Ring substituted chalcones were prepared
by condensation of the appropriate aromatic methyl
ketone and simple benzaldehyde. After purification,
they were obtained in moderate to good yields.The
structures of title compounds were characterized
spectral data (IR, 1H-NMR and Mass)
The IR spectra of the chalcones showed
Fig. 4. Binding mode of compound 3 h in the active
site of MAGL
bands due to absorption in the regions 1658-

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1672 cm-1 (C=O str), 1596-1620 cm-1 (C=C str).
In H-NMR spectra, the coupling constant for vinyl
7.25–7.86 (m, 10H, Ar-H& C=CHβ); MS: m/z 254
[M+1].
1
protons was found to be around 15.2-15.6 Hz,
confirming the trans-configuration of the prepared
chalcones. The aromatic protons showed signals
around 7.0-7.9 ppm. The Characteristic molecular
ion peaks were obtained [M+1]+ corresponding
to the molecular weights of the title compounds.
Compound -3f
3-(4-Hydroxyphenyl)-1-phenylprop-2-en-1-
one [R=OH]: IR ( νmax, cm–1): 1674 (C=O str), 1615
(C=C str);1H-NMR : 5.34 (s,1H,OH) 6.78-7.17
(d, 1H, CHα=C, J=15.6), 7.25–7.76 (m, 10 H , Ar-H&
C=CHβ); MS: m/z 225 [M+1]
1
Spectral data including IR, H-NMR and Mass of
the compounds were in good agreement with the
literature values26
Compound-3g
3-(4-Methoxyphenyl)-1-phenylprop-2-en-
1-one [R=4-OCH3]: IR ( νmax, cm–1): 1671 (C=O str),
1605 (C=C str);1H-NMR:3.01(s,3H, OCH3) 6.80-7.19
(d, 1H, CHα=C, J=15.6Hz), 7.25-7.76 (m, 10 H,
Ar-H& C=CHβ); MS: m/z 239 [M+1].
The synthesized chalcones (3a-j) were
tested for their central analgesic activities using hot
plate test and tail immersion tests at a dose of 50
mg/kg body weight.Tramodol was used as standard
drug for comparing the activity of chalcones.
Compound -3h
3-(3,4-Dimethoxyphenyl)-1-phenylprop-
2-en-1-one [R=3,4-(OCH3)2]: IR (νmax, cm–1): 1665
(C=O str), 1596 (C=C str); H-NMR: 3.05 (s, 6H,
(OCH3)2) 6.78-7.17 (d, 1H, CHα=C, J=15.6Hz),
7.25–7.76 (m, 10 H,Ar-H & C=CHβ); MS: m/z 269
[M+1].
Spectral data
Compound -3a
1
Chalcone [R=H]: IR ( νmax, cm–1): 1661
1
(C=O str), 1605 (C=C str); H-NMR : 6.58-6.97
(d, 1H, CHα=C J=15.6 Hz), 7.11-7.50 (d, 1H,
C=CHβ, J=15.6 Hz), 7.53–7.89 (m, 10H, Ar-H); MS:
m/z 209.1 [M+1]
Compound -3i
1-Phenyl-3-(3,4,5-trimethoxyphenyl)prop-
2-en-1-one [R=CH3]:IR ( νmax, cm–1):1658 (C=O str),
1621 (C=C str); 1H-NMR : 3.00 (s,6H,(OCH3)2) 3.04
(s,3H,OCH3) 6.67-7.06 (d, 1H, CHα=C, J=15.6Hz),
7.25–7.95 (m, 10 H, Ar-H& C=CHβ); MS: m/z 223
[M+1]
Compound -3b
3-(4-Fluorophenyl)-1-phenylprop-2-en-1-
one [R=F]: IR ( νmax, cm–1): 1672 (C=O str), 1620
1
(C=C str); H-NMR: 6.61-7.00 (d, 1H, CHα=C,
J=15.6Hz), 7.15-7.54 (d, 1H, C=CHβ, J = 15.6Hz),
7.59–8.01 (m, 9H, Ar-H); MS: m/z 227 [M+1]
Compound -3j
Compound -3c
1-Phenyl-3-p-tolylprop-2-en-1-one [R=CH3]:
FT-IR ( νmax, cm–1): 1660 (-C=O), 1606 (-C=C-);
1H-NMR : 1.12 (s, 3H, CH3), 6.38-6.77 (d,1H, CHα=C
J=15.2Hz), 7.25–7.76 (m, 10 H,Ar-H, & C=CHβ);MS:
m/z 223 [M+1]
3-(4-Chlorophenyl)-1-phenylprop-2-en-1-
one [R=Cl]: IR ( νmax, cm–1): 1668 (C=O str), 1615
(C=C str); H-NMR: 6.38-6.77 (d, 1H, CHα=C,
J=15.6Hz ), 6.89-7.28 (d, 1H, CH=CH, J = 15.6),
7.38–7.76 (m, 9H, Ar-H); MS: m/z 243 [M+1]
1
Central antinociceptive activity
Compound -3d
Ring substituted chalcones displayed
peripheral antinociceptive activity in acetic acid
induced writhing assay26. To evaluate their central
antinociceptive activity, tail immersion and hot plate
methods were used.
3-(2,5-Dichlorophenyl)-1-phenylprop-2-en-
1-one [R=2,5-(Cl)2]: IR (νmax, cm–1): 1659 (C=O str),
1596 (C=C str);1H-NMR : 6.89 -7.27(d, 1H, CHα=C,
J = 15.2 Hz), 7.36–8.12 (m, 9H,Ar-H& C=CHβ); MS:
m/z 277 [M+1]
Tail immersion test
Compound -3e
Results of the tail immersion assay showed
that most of the chalcones were active in this test.
The oral administration of compound 3 g and 3 h
3-(4-Nitrophenyl)-1-phenylprop-2-en-1-one
[R=NO2]:IR ( νmax, cm–1):1660 (C=O str), 1598 (C=C
str);1H-NMR:6.74-7.12 (d, 1H, CHα=C, J = 15.2 Hz),

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significantly increased the latency time (9.3 0.22
Hot plate test
Profile of antinociceptive activity of
chalcones in this assay showed that 3h showed
increased latency period up to 8.0 0.25 sec which is
almost comparable to latency of tramodol, 8.3 0.21
sec.The next chalcone which was active in this test
was 3i, 3, 4, 5-trimethoxy chalcone, which had the
latency of 7.2 0.25 sec.The results demonstrate that
halogen containing chalcones, 3b, 3c and 3d, which
were moderately active in tail immersion assay were
found to be moderately active even in hot plate test.
& 9.6 0.28 sec) to the nociceptive response in
this test comparable to that of standard drug
tramodol (11.5 0.32 sec). Unsubstituted chalcone,
3a, was found to be moderately active in this assay
(6.01 0.62 sec). Introduction of halogens such as
fluorine and chlorine improved the activity (7.0 0.22
&7.5 0.30 sec). Halogen containing chalcones
3b, 3c and 3d showed good activity in this assay
suggesting that presence of this halogen atom is
favourable for central antinociceptive activity.
The hot-plate test measures supraspinal
responses and the tail-immersion test measures
spinal level responses. Hence combined, they
represent good models for assessing the central
level antinociceptive activity31-33. Chalcones showed
marked activities in the hot-plate and in the
tail-immersion tests (Table. 3), suggesting that they
were able to cross blood brain barrier and active on
the central nociceptive pathways.
Presence of hydroxyl group on chalcone
was unable to exert any promising activity in this
assay (5.01 0.20 sec) whereas replacement
of hydroxy group with methoxy functionality
(3f) significantly improved the central antinociceptive
with latency period of 6.52 0.67 sec. Results of this
assay indicates ability of chalcones to act as central
antinociceptive agents.
Table 3: Antinociceptive activities of
substituted chalcones (3a-j) in different central
antinociceptive models
CONCLUSION
Chalcones, the small organic molecules
possess good binding affinity for MAGL enzyme,
derivative 3 h bearing methoxy group at both 3r d
and 4th positions showed highest affinity. Chalcones
possessing halogens 3b, 3c, 3d and methoxy groups
3f, 3g and 3 h exhibited good central analgesic
activity in tail immersion and hot plate methods and
highest activity was observed with derivative 3 g,
which showed high affinity for MAGL enzyme.
S.No.
Control
R
Tail immersion
test(Latency
Hot-Plate
test(Latency
period in sec.) period in sec.)
-
-
3.2 0.16
11.5 0.22*
6.01 0.62*
7.0 0.22*
7.5 0.30*
7.5 0.30*
6.01 0.62
5.01 0.20*
9.3 0.22 *
2.5 0.22
8.3 0.21
3.6 0.21*
5.3 0.21*
5.3 0.21*
4.3 0.22
3.6 0.21*
3.8 0.22*
5.3 0.24*
8.0 0.25*
7.2 0.25
3.8 0.22*
Tramadol
3a
3b
3c
3d
3e
3f
3g
3h
3i
4-H
4-F
4-Cl
2,5-(Cl)2
4-NO2
4-OH
4-OCH3
ACKNOWLEDGEMENT
We are grateful to Department of Science
&Technology- Consolidation of University Research
for Innovation and Excellence inWomen Universities,
Sri Padmavathi Mahila University, for providing FTIR
spectrum.
3,4-(OCH3)2 9.6 0.28*
3,4,5-(OCH3)3 7.5 0.30
3j
4-CH3
3.2 0.16*s
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