Novel quinoxalinyl chalcone hybrid scaffolds as enoyl ACP reductase inhibitors: Synthesis, molecular docking and biological evaluation

Article abstract of DOI:10.1016/j.bmcl.2017.03.059

We report herein, first ever synthesis of series of novel differently substituted quinoxalinyl chalcones using Claisen Schmidt condensation, its molecular docking studies, and potential to be good anti-microbial, anti-tubercular and anti-cancer agents. Th

Full text of DOI:10.1016/j.bmcl.2017.03.059

Accepted Manuscript
Novel quinoxalinyl chalcone hybrid scaffolds as enoyl ACP reductase inhibi-
tors: Synthesis, molecular docking and biological evaluation
Vidya Desai, Sulaksha Desai, Sonia Naik Gaonkar, Uddesh Palyekar, Shrinivas
D. Joshi, Sheshagiri K. Dixit
PII:
S0960-894X(17)30308-6
DOI:
http://dx.doi.org/10.1016/j.bmcl.2017.03.059
BMCL 24811
Reference:
Bioorganic & Medicinal Chemistry Letters
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Revised Date:
Accepted Date:
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10 March 2017
22 March 2017
Please cite this article as: Desai, V., Desai, S., Gaonkar, S.N., Palyekar, U., Joshi, S.D., Dixit, S.K., Novel
quinoxalinyl chalcone hybrid scaffolds as enoyl ACP reductase inhibitors: Synthesis, molecular docking and
biological evaluation, Bioorganic & Medicinal Chemistry Letters (2017), doi: http://dx.doi.org/10.1016/j.bmcl.
2017.03.059
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Novel quinoxalinyl chalcone hybrid scaffolds
as enoyl acp reductase inhibitors: Synthesis,
molecular docking and biological evaluation
Vidya Desaia,*, Sulaksha Desaia , Sonia NaikGaonkara , Uddesh Palyekara, Shrinivas D. Joshib and
Sheshagiri K. Dixitb

Bioorganic & Medicinal Chemistry Letters
journal homepage: www.els evier.com
Novel quinoxalinyl chalcone hybrid scaffolds as enoyl ACP reductase inhibitors:
Synthesis, molecular docking and biological evaluation
Vidya Desaia,*, Sulaksha Desaia , Sonia Naik Gaonkara , Uddesh Palyekara, Shrinivas D. Joshib and
Sheshagiri K. Dixitb
aDnyanprassarak Mandal’s College and Research Centre, Assagao, Mapusa- Bardez, Goa and 403507, India
b Novel Drug Design and Discovery Laboratory, Department of Pharmaceutical Chemistry, S.E.T.’s College of Pharmacy, Sangolli Rayanna Nagar, Dharwad,
580002, India
ARTICLE INFO
ABSTRACT
Article history:
Received
Revised
Accepted
Available online
We report herein, first ever synthesis of series of novel differently substituted quinoxalinyl
chalcones using Claisen Schmidt condensation, its molecular docking studies, and potential to
be good anti-microbial, anti-tubercular and anti-cancer agents. The antimicrobial studies were
carried out against Staphylococcus aureus, Escherichia coli and Candida albicans using disc
diffusion procedure. The selected chalcones were tested for anti-cancer and cytoxicity activity
against MCF-7 cancer cell line using MTT assay method. All the synthesized compounds were
screened for in vitro anti-tubercular screening against MtbH37RV strains by Alamar blue dye
method. These results were compared with molecular docking studies carried out on
Mycobacterium tuberculosis enzyme enoyl ACP reductase using Surflex-Dock program that is
interfaced with Sybyl-X 2.0. SAR analysis for antimicrobial and antitubercular activity has also
been proposed.
Keywords:
Quinoxaline
Chalcones
Anti-tubercular
Anti-cancer
Molecular Docking
2009 Elsevier Ltd. All rights reserved
.
One of the major advances in the field of medicinal chemistry
and drug discovery has been the molecular hybridization
approach. This has risen from “drug evolution”, which drug-
drug hybridization is leading to drug molecules of potential
bioactivity. Konishi et al reported hybridization of Benzocaine
and Metoclopramide leading to generation of 16 new molecules1.
The large number of libraries of compounds is an encouragement
in the findings for new drug candidates. In the same lines,
molecular hybridization is a tool in drug designing, wherein
simples molecules can be linked together to construct new hybrid
molecules of varied biological interest2. This versatile approach
of designing new drug entities is the key to achieving large
number of hybrid molecules having better affinity and efficacy
than the parent molecule from which they are derived. One of the
pharmacophoric moieties, which have been more often the target
of medicinal chemists has been naturally occurring as well as
synthesized. Chalcones are biologically important α, β-
unsaturated carbonyl compounds, which as excellent building
blocks to heterocycles has attracted organic as well as medicinal
chemists3. Chalcone derivatives have been demonstrated to have
wide range of biological activities4-5. Chalcone linked hybrids
with heterocycles is a step towards achieving new drug targets6,
for example coumarinyl-chalcone hybrids as a promising
bioactive agents showing wide spectrum of biological
properties7, novel chalcone-thiazole hybrids as having high
antibacterial action against Staphylococcus aureus, making it a
potential candidate to act as antibiotic8. Variety of chalcone
hybrids having naphthyl, isoxazolyl and indolyl moieties have
been known to show potency as anticancer agents9-11.N-
heterocyclic chalcones have been known in literature, and have
been biologically evaluated for their anti-microbial and anti-
tubercular activity12-14
.
Tuberculosis (TB) is a highly dreaded, chronic, infectious, air-
borne disease affecting more than two million people all around
the world and with more than 8 million cases every year15. Due to
emergence of multi-drug resistant varieties of Mycobacterium
tuberculosis and aids epidemic, drugs like isoniazid, rifampicin,
pyrazinamide, ethambutol are no more effective16. There are
several promising clinical trials development programs carried
out to conduct evaluation of new anti-TB drugs, such as PA-824,
which is a nitroimidazooxazine, an anti-TB drug candidate in the
late stage clinical development, showing increased activity
against Mycobacterium tuberculosis. However, there are few
novel compounds known to hit the target. Numbers of chalcones
are known to show high inhibitory activity against the growth of
in vitro Mycobacterium tuberculosis H37Rv strains, when used
in low concentrations17. Quinoxaline, a bicyclic nitrogen
heterocycle is said to have enough potential to be explored for
biological evaluation18. Various derivatives of quinoxaline are
known to possess wide range of biological activities ranging

from anti-microbials, anti-tubercular, kinase inhibitors, anti-viral,
anti-inflammatory, analgesics, anticancer, anxiolytics,
Table 1 Claisen Schmidt condensation of quinoxaline-2-
carbaldehyde with various acetophenones to give chalcones 2
a-n
antihelmintics, anticonvulsants, antioxidants, antidepressant, anti-
hypertensives to antiHIVs19-22. Thus, being a part of well-known
antibiotics, like echinomycin laevomycin and actinoleutin, the
substituted quinoxaline skeleton need to be exploited more in
drug discovery23.
Compound
Timea
Yieldb in % Melting PointoCc
2a
2b
2c
2d
2e
2f
2
2
2
4
3
2
2
2
2
4
2
2
2
2
78
75
80
85
75
80
65
80
95
70
75
60
60
90
256-258
182-185
124-126
98-100
The combination of these properties of quinoxaline and
chalcone in one compound would lead to a drug with potent
bioactivity. Molecular hybridization approach from quinoxaline
and chalcone include novel 2-acetylquinoxaline derived-
chalcones which exhibited in vitro glioma cell proliferation
activity24. Quinoxaline-6-carbaldehyde have also been converted
to chalcones using aromatic aldehydes and evaluated for breast
cancer25. Quinoxaline derived chalcones has been synthesized
126-128
135-138
150-152
144-146
120-122
136-138
156-158
164-167
205-207
130-132
2g
2h
2i
and biologically evaluated26-27
.
Chalcone derivatives of
quinoxaline-1, 4-dioxides have been screened as anti-TB
agents28. In his PhD thesis, Mohan et al has reported work on
synthesis and reactions of quinoxalines involving preparation of
quinoxaline-2-carbaldehyde29. Interestingly, in literature,
quinoxaline-2-carbaldehyde has not been exploited and there are
no reports on anti-tubercular activity of quinoxalinyl chalcones.
In view of this, an approach was designed to get a quinoxalinyl
chalcone hybrid molecule from acetophenones and quinoxaline-
2-carbaldehyde and study its potential as antitubercular agents.
(Fig.1.)
2j
2k
2l
2m
2n
aTime taken for completion of the reaction monitored by thin
layer chromatography.
bCalculated from the amount of chalcone obtained after
recrystallization.
cDetermined using thiels tube paraffin method.
The first six compounds 2a-f have been reported by us27, but
their molecular docking studies and biological activities have
been performed now. The acetophenones (1 equivalent) was
treated with aqueous ethanolic solution of sodium hydroxide,
stirred at room temperature for 10 minutes for enolate formation,
then to quinoxaline-2-carbaldehyde (1 equivalent) was added and
the stirring continued till the completion of the reaction, which
was monitored by thin layer chromatography. The reaction was
worked up by addition ice and hydrochloric acid. The solid
product filtered, was purified by recrystallization using ethanol.
All the synthesized compounds have been identified and
Fig. 1. Molecular hybridisation of quinoxaline and chalcones having drug
potency
Quinoxaline-2-carbaldehyde was first synthesized by literature
known procedure from glucose, phenylenediamine, hydrazine to
form an intermediate, followed by oxidation using sodium
metaperiodate29. This was then reacted with substituted aromatic
acetophenones under Claisen Schmidt condensation basic
reaction conditions30-31 to give corresponding chalcone
derivatives 2a-n in moderate to good yields (Scheme 1, Table 1).
In all 14 quinoxalinyl chalcone derivatives were synthesized.
1
confirmed by FTIR, HNMR and 13CNMR spectroscopy. The
purification of the compounds was confirmed by mass spectral
analysis and by HPLC measurements on CXTH-3000
Chromatography
Data
Handling
System
(Analytical
Technologies Limited). Chromatographic separation was
achieved at ambient temperature by using mobile phase
consisting of methanol and water in the ratio 90:10 (v/v) by 20
min. The mobile phase was pumped at the rate of 1.0mL/min.
The detector wavelength was set at 370nm.The run time was set
at 20min and retention time of all chalcones was between 16-22
min. The purity of all the synthesized compounds was found to
be 95% and above. The chromatogram of chalcone is shown in
fig 2. We were successful in achieving synthesis of new
quinoxalinyl chalcone hybrids bearing different substituents.
That gave us an opportunity to explore the applications of such
chalcones for antimicrobial, anticancer and anti-tubercular
activity, as well predict structure activity relationships (SAR
analysis).
Scheme 1. Synthetic route towards quinoxalinyl chalcones
from glucose (2a-n) Reagents and conditions: (a) H2O,
o-phenylene diamine, glacial CH3COOH, NH2-NH2.H2O,
reflux, 5 hours, cool in icebath; (b) H2O, NaIO4, glacial
CH3COOH, stir, r.t. 16 hours; (c) Aromatic ketones, NaOH,
H2O, EtOH, stir, r.t.; (d) Ice, concentrated HCl
Antibacterial and antifungal activities of the newly
synthesised quinoxalinyl chalcone derivatives 2a-n were
determined using agar well disc diffusion procedure32. In brain
heart infusion agar, against gram positive strain Staphylococcus

aureus and gram negative strains Escherichia coli, and in
sabouraud agar medium against fungal organism Candida
albicans. Five wells were made on each plate and 75µL, 50µL,
25µL, 10µL and 5µL of compound were added into the
respective wells. Plates were incubated for 18- 24 hrs at 37oC in
incubator. Diameter of inhibition zone to nearest whole
millimeter was measured by holding the measuring device.
Ciprofloxacin and fluconazole was used as standard drug. (Table
2)
bacterial but no antifungal activity, while compound 2h (3-OH)
exhibits both antibacterial as well as antifungal activity. This was
also evident with the comparison of activity of 2c and 2i which
contains (p-Br) and (m-Br) substituents respectively. Significant
antibacterial and antifungal activity for 2n, containing naphthyl
group as compared to 2j containing phenyl group, indicates that
increase in hydrophobicity has positive effect on activity.
Replacement of phenyl ring 2j by a heterocyclic pyridinyl ring 2g
does not show change in activity.
Table 2 Anti-microbial activity of synthesized quinoxalinyl
chalcones 2a-n
Compound Ar
Minimum inhibitory
concentration-MIC (µg/mL)
S. aureus E. coli C. albicans
2a
2b
2c
2d
2e
2f
4-Hydroxyphenyl
5
5
4-Aminophenyl
4-Bromophenyl
50
75
25
25
25
10
25
25
5
25
75
25
25
25
50
10
25
25
25
50
25
25
-
4-Methoxyphenyl 50
4-Chlorophenyl
4-Fluorophenyl
4-Pyridinyl
25
75
50
Fig.2. Representative Chromatogram of chalcone
The cytotoxicity of selected compounds 2a, 2b and 2f (Table
3) was evaluated using standard MTT assay33. In this assay, the
reduction of yellow 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl
tetrazolium bromide was measured by mitochondrial succinate
dehydrogenase. The cell line used was MCF-7 cell line, a
Michigan cancer foundation-7 cell line, a Human mammary
gland adenocarcinoma, which was procured from National
Centre for Cell Science (NCCS), Pune, India. IC50 is Half
maximal inhibitory concentration, at which 50% of cells were
undergoing cytotoxic cell death due to synthesized compounds
treatment. Cis-Platin and Doxorubicin was used as standard
drugs. Absorbance is measured at wavelength of 570nm by using
LISA plus.
2g
2h
2i
3-Hydroxyphenyl 10
3-Bromophenyl
Phenyl
25
50
50
50
50
25
2
5
2j
50
25
25
25
25
2
2k
2l
3-aminophenyl
4-Nitrophenyl
3-Nitrophenyl
Naphthyl
2m
2n
Ciprofloxacin
Fluconazole
-
-
16
Table 3 Preliminary cytotoxicity screening of quinoxalinyl
chalcones 2a, 2b and 2f
Sample
Conc. Absorbanced Result
µg/m
L
IC50
µg
2a
10
20
30
40
50
10
20
30
40
50
10
20
30
40
50
0.584
0.581
0.420
0.399
0.386
1.772
1.772
1.631
1.631
1.585
0.836
0.644
0.505
0.477
0.380
No lysis
No lysis
No lysis
-
No lysis
No lysis
2b
2f
Partial lysis
Partial lysis
50% lysis
>50% lysis
>50% lysis
No lysis
25
50
From the outcomes of the antimicrobial activity of the
synthesized quinoxalinyl chalcone derivatives, the following
structure activity relationships (SAR) can be established. Overall,
the quinoxalinyl chalcones 2a-n exhibit better antibacterial
activity against gram-ve bacterial strains as compared to gram+ve
bacterial strains. The best activity against gram-ve and gram +ve
bacterial strains for compounds 2a and 2h indicates that presence
of –OH substituent, is necessary for enhanced antibacterial
activity. The position of OH substituent also decides the
specificity. In case of compound 2a (4-OH) exhibits anti-
No lysis
No lysis
No lysis
No lysis

Cis-platine
Doxorubicine
50% lysis
50% lysis
7.5
A blue color in the well was interpreted as no bacterial growth,
and pink color was scored as growth. The MIC was defined as
lowest drug concentration which prevented the color change from
blue to pink. (Fig.3.)
5-7.5
The IC50 (half maximal inhibitory concentration) value was
determined in case of each compound. The least concentration to
show 50% inhibition of cell line was found to be 25µg in case of
compound 2b containing –NH2 substituent and 50µg in case of
compound 2f containing halogen substituent whereas, compound
2a was found to be inactive against MCF-7 cell lines. Compound
2a containing OH substituent showed no activity.
Fig. 3. To the left shows the MIC values for the standard drugs,
Streptomycin, Pyrazinamide and Ciprofloxacin, while that to the right
shows the MIC values for the synthesized quinoxalinyl chalcones; MIC
value 3.12µg/mL (2 and 6) is for chalcones 2a and 2h, containing the –
OH substituent.
The newly synthesized chalcones 2a-n has been screened for
their in vitro anti-tubercular activity using Alamar Blue Dye
method34, this methodology is non-toxic, uses thermally stable
reagents and showed good correlation with the proportional and
BACTEC radiometric method. The mycobacterium tuberculosis
strain used was MtbH37Rv, while the standard drugs were
Streptomycin, Pyrazinamide, and Ciprofloxacin. (Table 4)
From the observations of in vitro anti-tubercular results for
the synthesized quinoxalinyl chalcones, following structure-
activity relationships (SAR) can be predicted. The maximal
activity exhibited by compounds 2a and 2h, is comparable to the
standard drugs Pyrazinamide and Ciprofloxacin, indicates that
presence of –OH substituent increases the anti-tubercular
activity. Replacement of phenyl ring in 2j by heterocyclic
pyridinyl ring in 2g increases the potency of the compound for
anti-tubercular activity. Presence of halogens, methoxy, amino,
nitro groups had no significant effect on the anti-tubercular
activity. Replacement of phenyl ring in 2j by naphthyl ring in 2n
decreases the potency of the compound for anti-tubercular
activity, indicating that lipophilicity has adverse effect on the
activity.
Table 4 In vitro antitubercular activity of synthesized
quinoxalinyl chalcones 2a-n
Sample
Ar
Minimum inhibitory
concentration-MIC
(µg/mL)
MtbH37RV
2a
2b
2c
2d
2e
2f
4-Hydroxyphenyl
4-Aminophenyl
4-Bromophenyl
4-Methoxyphenyl
4-Chlorophenyl
4-Fluorophenyl
4-Pyridinyl
3.12
25
50
25
To generalize the innovative approaches to drug targets, the
study related to biology of Mycobacterium tuberculosis becomes
a key component. Among the several drug targets known for
tuberculosis [35-36], the cell wall biosynthesis related drug target
is the most promising one, since their biosynthetic enzymes do
not have homologues in the mammalian system. One of the
major drug targets for Mycobacterium tuberculosis has also been
mycolic acid [37]. Mycolic acid, forms an important fatty acid,
and a main constituent of the mycobacterial cell wall, which is
present in fatty acid synthase system of Mycobacterium
tuberculosis. The mycolic acid biosynthesis has been carried out
by many successsive enzyme catalyzed cycles equivalent to Fatty
Acid Synthase (FAS) systems. The enzyme InhA, which is an
enoyl acyl carrier protein reductase from Mycobacterium
tuberculosis is the key enzyme for the synthesis of type II fatty
acid system, which catalyzes NADH-dependent reduction of 2-
trans-enoyl-ACP (acyl carrier protein) which is an acyl carrier
protein, to yield NAD and reduced enoyl thioester-ACP
substrate, which is responsible for the synthesis of mycolic acid.
This has been the drug targets for well known anti-Tb drugs like
Isoniazid (INH) and Ethionamide [38]. Chalcones derived enoyl
ACP reductase inhibitors have been studied and proved to have
high binding affinity to the enzymes wherein the main
influencing factors of molecular interaction between ENR and
chalcone derivatives determined by this study were H-bond,
hydrophobic and electrostatic interaction. [39] So, we chose
enzyme enoyl ACP reductase for our molecular docking studies
on quinoxalinyl chalcones. The crystal structures used were
Mycobacterium tuberculosis enoyl reductase (InhA) complexed
with 1-cyclohexyl-N-(3,5-dichlorophenyl)-5-oxopyrrolidine-3-
carboxamide (PDB ID: 4TZK) for the docking studies, obtained
from the Protein Data Bank. The protein was prepared for
docking by adding polar hydrogen atom with Gasteiger-Huckel
charges [40] and the molecular docking was performed with
Surflex-Dock program that is interfaced with Sybyl-X 2.0. [41].
25
25
2g
2h
2i
6.25
3.12
25
3-Hydroxyphenyl
3-Bromophenyl
Phenyl
2j
25
2k
2l
3-aminophenyl
4-Nitrophenyl
3-Nitrophenyl
Naphthyl
25
25
2m
2n
25
25
Streptomycind
6.25
Ciprofloxacind
Pyrazinamided
3.12
3.12

-60.01
-49.13
-37.36
-64.81
-175.74
-173.90
-209.00
-225.27
-38.99
-33.28
-35.93
-46.90
The molecular docking study [42] revealed that 2a and 2h acts as
very good inhibitor of enoyl ACP reductase enzyme. As depicted
in fig. 4, compound 2a, makes one hydrogen bonding interaction
at the active site of the enzyme (PDB ID: 4TZK), Hydrogen atom
of hydroxyl group at 4th position of aromatic ring makes an
hydrogen bonding interaction with oxygen of NAD500 (O-H -----
O-NAD500, 1.86 Å). Table 5 depicts the results of docking
studies. As depicted in the fig. 5., compound 2h makes five
hydrogen bonding interaction at the active site of the enzyme
(PDB ID: 4TZK), among them three interactions are came from
the hydrogen of the hydroxyl group present at 3rd position of
aromatic ring, with oxygen of NAD500 and THR196 (O-H -----
O-NAD500, 1.81 & 2.71 Å; HG-THR196, 2.34 Å) and remaining
two interactions raised from the oxygen of carbonyl group with
hydrogen of NAD500 & TYR158 (C=O ----- H-NAD500, 1.88
Å; H-TYR158, 2.00 Å).
2k
2l
5.34
4.10
4.81
6.11
-0.88
-0.62
-1.37
-2.11
0.84
0.00
0.00
1.15
-115.44
-118.93
-132.45
-145.14
2m
2n
aC Score (Consensus Score) integrates a number of popular scoring
functions for ranking the affinity of ligands bound to the active site of a
receptor and reports the output of total score;
bCrash-score revealing the inappropriate penetration into the binding
site. Crash scores close to 0 are favorable. Negative numbers indicate
penetration.
cPolar indicating the contribution of the polar interactions to the total
score. The polar score may be useful for excluding docking results that
make no hydrogen bonds.
dD-score for charge and van der Waals interactions between the protein
and the ligand.
ePMF-score indicating the Helmholtz free energies of interactions for
protein-ligand atom pairs (Potential of Mean Force, PMF).
fG-score showing hydrogen bonding, complex (ligand-protein), and
internal (ligand-ligand) energies.
gChem-score points for H-bonding, lipophilic contact, and rotational
entropy, along with an intercept term.
Fig.4. Interaction of 2a at the binding active site of the enzyme enoyl acp
reductase (PDB ID: 4TZK). Ligand and key residues are represented as
stick models and coloured by atom type, here the proteins are
represented by red dotted lines. White: hydrogen atom; red: oxygen
atom; dark blue: nitrogen atom; blue: the backbone and carbon atom of
compound 2a. Quinoxalinyl moiety of compound 2a embedded in the
binding pocket of enoyl ACP reductase. Hydrogen atom of hydroxyl
group at 4th position of aromatic ring makes an hydrogen bonding
interaction with oxygen of NAD500.
Fig.6. Quinoxalinyl chalcone 2a and 2h, containing –OH substituent
shows significant antitubercular activity against MTbH37RV, Chalcone
2a also exhibits specific antibacterial activity against both gram+ve as
well as gram –ve bacteria and no activity against antifungal activity,
while chalcone 2h showed both antibacterial as well as antifungal
activity.
Fig.5. Docked view of compound 2h at the active site of the enzyme PDB
ID: 4TZK. Compound 2h makes five hydrogen bonding interaction at
the active site of the enzyme (PDB ID: 4TZK), among them three
interactions are came from the hydrogen of the hydroxyl group present
at 3rd position of aromatic ring.
In conclusion, this work on newly synthesized quinoxalinyl
chalcones investigates, the role of quinoxalinyl chalcone moiety
as a versatile pharmacophoric unit, having range of biological
activities. The study tells us about how molecular hybridisation of
quinoxaline and chalcone can be exploited to search novel drug
targets to treat highly dreaded diseases like tuberculosis and
cancer. The MTT assay studies revealed that chalcone 2b,
containing the –NH2 group, exhibit good anticancer activity. The
chalcone 2a, containing the –OH group showed specifically anti-
bacterial and in vitro antitubercular activity, but no anticancer
activity. The good inhibitory action of quinoxalinyl chalcones 2a
and 2h towards the enzyme enoyl ACP reductase, has been an
additive research on such chalcones. The wide array of
bioactivities exhibited by quinoxalinyl chalcones, reflects the
importance of such heterocyclic moiety in designing novel drug
targets in drug development. This novel findings has thrown light
on how a simple quinoxalinyl chalcone hybridisation can lead to a
potential moiety as targets to develop new drug entities. Further,
such chalcones can be excellent building blocks to heterocycles
with great diversity, a heterocyclic scaffold, having varied
biological applications.
Table 5 Surflex Docking score (kcal/mol) of the lists of
quinoxalinyl chalcones (2a-n)
PMF
Scoree
G
Scoref
Chem
Scoreg
C
Scorea
Crash
Scoreb
Polar
Scorec
D
Scored
Code
-74.20
-53.35
-59.66
-222.05
-161.40
-134.90
-45.17
-34.34
-39.40
2a
2b
2c
6.97
4.08
5.56
-1.28
-0.62
-0.65
3.03
0.00
1.91
-140.48
-110.13
-117.88
-58.88
-57.18
-61.87
-44.64
-205.39
-131.25
-125.36
-184.05
-44.61
-39.22
-36.89
-34.59
2d
2e
2f
6.29
5.67
5.65
5.28
8.02
4.97
-1.37
-0.51
-0.51
-0.81
-1.71
-0.73
2.91
1.93
1.82
0.00
2.97
1.81
-127.33
-115.39
-109.28
-118.75
-137.23
-117.07
2g
2h
2i
-57.94
-67.96
-218.32
-143.90
-45.35
-40.66
2j
5.99
-1.20
1.82
-122.92
-44.00
-168.55
-39.99

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H. Van Boom, A. Rich, Nucleic Acids Research. 1985, 13, 2305–
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Acknowledgments
This work was supported by the Department of Science and
Technology-Government of Goa, India (No. 6-162-2013/STE-
DIR/Acct/556). The authors acknowledge the support of the
management of Dnyanprassarak Mandal’s College and Research
Centre, Assagao-Goa, India, for providing laboratory facilities.
The authors are also grateful to Centaur Drug House, for
providing active pharmaceutical ingredient Ibuprofen. The
authors thank Goa University, Goa and Sophisticated Analytical
Instrumentation Facilities (SAIF), Chandigarh, Punjab, India for
spectral facilities and Maratha Mandal’s NGH Institute of Dental
Sciences and Research Centre, Belgaum, Karnataka, India for
biological screening facilities.
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ligands was generated by the SKETCH module implemented in
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minimized conformation was obtained with the help of the Tripos
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Supplementary Details
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