WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

Kanakaraju et al.

World Journal of Pharmacy and Pharmaceutical Sciences

SJIF Impact Factor 5.210

Volume 4, Issue 09, 620-633

Research Article

ISSN 2278 4357

COMPUTER AIDED LIGAND DESIGN AND MOLECULAR DOCKING

STUDIES ON A SERIES OF PYRIDINE-CHALCONE CONJUGATES
AGAINST SELECTED ANTITUBERCULAR DRUG TARGETS
Asst. Prof. A. Kanakaraju1,* and Prof. Y. Rajendra Prasad2
1

Pharmaceutical Chemistry Division, Vignan Institute of Pharmaceutical Technology, Beside

SEZ, Duvvada, Visakhapatnam, Andhra Pradesh, Pincode-5530049, India.
2

Pharmaceutical Chemistry Division, A U College of Pharmaceutical Sciences, Andhra

University, Visakhapatnam, Andhra Pradesh, Pincode-530003, India.

Article Received on
25 July 2015,
Revised on 16 July 2015,
Accepted on 07 Aug 2015

ABSTRACT
Contemporary scenario of drug discovery and development there is an
accumulation

of

diseases

through

more-complex

pathological

mechanisms, for which the classic single target, single drug pattern
has moderately or completely ineffective. In these conditions, drugs

*Correspondence for

acting on various targets could offer greater efficacy profiles compared

Author
Prof. A. Kanakaraju

with single-target drugs. Hence in the present research as a part of our

Pharmaceutical Chemistry

ongoing search for new chemical entities as potential antitubercular

Division, Vignan Institute

agents, we could design a series of pyridine-chalcone conjugates to

of Pharmaceutical

study their inherent mechanism against selected antitubercular drug

Technology, Beside SEZ,

target by using molecular docking studies.

Duvvada, Visakhapatnam,
Andhra Pradesh, Pincode-

KEYWORDS: Pyridine-chalcone conjugates, antitubercular drug

5530049, India

target, molecular docking.

1. INTRODUCTION
In the recent past three decades, molecular docking methodologies have become well
integrated in the modern drug design process and have gained in influence. They have
dramatically revolutionized the way in which we approach drug discovery, leading to the
explosive growth in the amount of chemical and biological data that are typically
multidimensional in structure. A variety of advanced computational algorithms and methods
has been effectively applied recently in medicinal chemistry for dimensionality reduction and

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visualization of the chemical data of different types and structure.[1-5] The majority of these
computational models are commonly based on the basic principles of dimensionality
reduction and mapping. In turn, dimensionality reduction is an essential computational
technique for the analysis of a large-scale, streaming and tangled data. In silico methods may
benefit drug discovery and development significantly by saving an average of $130 million
and 0.8 years per drug. In an industrial environment, the commonly used ligand-based and
receptor-based methods need to be computationally faster to return the utmost benefit.
Intelligent database searching using new fast feedback driven screening methods appears to
be particularly rewarding in terms of both cost and time benefits6. Consequently it was
considered worthwhile to discover a drug based on modern computational methods such as
molecular docking, pharmacophore modeling and quantitative structure activity relationship
studies etc. Homosapiens battle with tuberculosis (TB) dates back to ancient times. TB,
which is caused by Mycobacterium tuberculosis (Mtb), was a much more widespread disease
in the past than it is today, and it was responsible for the deaths of about one billion people
during the last two centuries. The introduction of TB chemotherapy in the 1950s, along with
the pervasive use of BCG vaccine, had a great impact on further reduction in TB incidence.
However, despite these advances, TB still remains a leading infectious disease worldwide.
The increasing emergence of drug-resistant TB, especially multidrug-resistant TB (MDR-TB,
resistant to at least two frontline drugs such as isoniazid and rifampin), is particularly
frightening. In view of this situation, the World Health Organization (WHO) in 1993 declared
TB a global emergency. There is an urgent need to develop new anti-TB drugs. However, no
new TB drugs have been developed in about 40 years. Although TB can be cured with the
current therapy, the six months needed to treat the disease is too long, and the treatment often
has significant toxicity.[7, 8] Therefore in the present study we could have developed a series
of some new pyridine-chalcone conjugates

and established their binding orientation,

chemical reactivity and mechanism of binding against selected ten vital anti-TB drug targets
which are involved in the Mycobacterium tuberculosis cell cycle, cell growth and replication,
They are Shikimate Kinase (SK)[9], Chorismate Synthetase (CS)[10], Isocitratelyase (ICL)[11],
Pantothenate Synthetase (PS)[12], Enoyl-[Acyl-Carrier Protein] Reductase (InhA)[13], 3Oxoacyl-[Acyl-Carrier Protein] Reductase (MabA)[14], Ornithine Acetyltransferase (OAT)[15],
Lumazine Synthetase (LS)[16], Quinolinate Phosphoribosyl Transferase (QAPRT)[17] and
Glucosamine-1-Phosphate-N-Acetyl Transferase (GLmU)[18], respectively.

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2. MATERIALS AND METHODS

2.1. Software Methodology
In the present study, software Molegro Virtual Docker (MVD) v 5.0 (www.molegro.com)
along with Graphical User Interface (GUI), MVD tools was utilized to generate grid,
calculate dock score and evaluate conformers. Molecular docking was performed using
MolDock docking engine of software. The scoring function used by MolDock is derived from
the Piecewise Linear Potential (PLP) scoring functions. The active binding site region was
defined as a spherical region which encompasses all protein within 15.0 Ao of bound
crystallographic ligand atom with selected co-ordinates of X, Y and Z axes, respectively.
Default settings were used for all the calculations. Docking was performed using a grid
resolution of 0.30 Ao and for each of the 10 independent runs; a maximum number of 1500
iterations were executed on a single population of 50 individuals. Both the active binding
sites and ligands were treated as being flexible i.e. all non-ring torsions were allowed.[19]
2.2. Molecular Modeling
A set of some novel pyridine-chalcone conjugates listed in Table 3 and 4, were designed and
modeled based on the synthetic chalcones which earlier synthesized and reported from
Andhra University, Pharmaceutical Chemistry Research Laboratories as potential
antitubercular agents.[20] Correspondingly, a database of thirty five pyridine-chalcone
conjugates were modeled by using ISIS DRAW 2.2 software and subjected for ligand
preparation protocol.
2.3. Ligand Preparation
The structures of pyridine-chalcone conjugates were converted into suitable chemical
information using Chemdraw ultra v 10.0 (Cambridge software), copied to Chem3D ultra v
10.0 to create a 3D model and, finally subjected to energy minimization using molecular
mechanics (MM2). The minimization was executed until the root mean square gradient value
reached a value smaller than 0.001kcal/mol. Such energy minimized structures are considered
for docking and corresponding pdb files were prepared using Chem3D ultra v 10.0 integral
option (save as /Protein Data Bank (pdb)) (Table 3 and 4).[21]
2.4. Protein Selection: The selection of target protein for molecular docking studies is based
upon several factors i.e. structure should be determined by X-ray diffraction, and resolution
should be between 2.0-2.5Ao, it should contain a co-crystallized ligand; the selected protein
should not have any protein breaks in their 3D structure.

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ramachandran plot statistics as the important filter for protein selection that none of the
residues present in disallowed regions.[22]
2.5. Protein Preparation
Table 1: Selected Antitubercular Drug Targets.
Name of the Antitubercular Target Protein
Shikimate Kinase (SK)
Chorismate Synthetase (CS)
Isocitratelyase (ICL)
Pantothenate Synthetase (PS)
Enoyl-[Acyl-Carrier Protein] Reductase (InhA)
3-Oxoacyl-[Acyl-Carrier Protein] Reductase (MabA)
Ornithine Acetyltransferase (OAT)
Lumazine Synthetase (LS)
Quinolinate Phosphoribosyl Transferase (QAPRT)
Glucosamine-1-Phosphate-N-Acetyl Transferase (GLmU)

PDB ID
1L4Y
2QHF
1F8I
1N2H
2X22
1UZN
3IT4
2C9D
1QPN
3D8V

All the X-ray crystal structures of the selected target proteins were obtained from the
Brookhaven Protein Data Bank (http://www.rcsb.org/pdb). Subsequent to screening for the
above specific standards the resultant protein targets (Table 1) were prepared for LPIIFD
simulation in such a way that all heteroatoms (i.e., non-receptor atoms such as water, ions,
etc.) were removed and Kollmann charges were assigned.[23]
2.6. Software Method Validation
Table 2: Software Validation Data.
PDB ID
1L4Y
2QHF
1F8I
1N2H
2X22
1UZN
3IT4
2C9D
1QPN
3D8V

Co-Crystallized Ligand Code

CL191
NA602
GLV461
PAJ10002
NAD1270
NAP1249
GOL500
PHR791
NCN2901
UD1496

RMSD (Ao)
1.42
1.22
1.71
1.27
0.92
1.32
1.22
1.18
1.77
1.24

Software method validation was performed in MVD using Protein Data Bank (PDB) proteins
1L4Y, 2QHF, 1F8I, 1N2H, 2X22, 1UZN, 3IT4, 2C9D, 1QPN and 3D8V. The x-ray crystal
structures of 1L4Y, 2QHF, 1F8I, 1N2H, 2X22, 1UZN, 3IT4, 2C9D, 1QPN and 3D8V
complex with co-crystallized ligands were recovered from http://www.rcsb.org/pdb. The bio
active co-crystallized bound ligands were docked with in the active site region of 1L4Y,

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2QHF, 1F8I, 1N2H, 2X22, 1UZN, 3IT4, 2C9D, 1QPN and 3D8V, respectively. The RMSD
of all atoms between the docked and X-ray crystallographic conformations are displayed in
the following Table 2. The results indicating that the parameters for docking simulation are
good in reproducing X-ray crystal structure.
2.7. Molecular Docking
In the present investigation, we make use of a docking algorithm called MolDock. MolDock
is based on a new hybrid search algorithm, called guided differential evolution. The guided
differential evolution algorithm combines the differential evolution optimization technique
with a cavity prediction algorithm.[24,25]
Table 3: Pyridine-chalcone conjugates (KR1-KR35) with their Moldock Scores
(kcal/mol) against selected antitubercular drug targets.

Compound
KR1
KR2
KR3
KR4
KR5
KR6
KR7
KR8
KR9
KR10
KR11
KR12
KR13
KR14
KR15
KR16
KR17
KR18
KR19
KR20
KR21

R
Phenyl
2-MeC6H4
3-MeC6H4
4-MeC6H4
2-OMeC6H4
3-OMeC6H4
4-OMeC6H4
3-OHC6H4
4-OHC6H4
3,5-diOHC6H3
4,5-diOHC6H3
2-Me,5-OHC6H3
2-NH2C6H4
3-NH2C6H4
4-NH2C6H4
2-NO2C6H4
3-NO2C6H4
4-NO2C6H4
2-ClC6H4
3-ClC6H4
4-ClC6H4

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SK
-92.2807
-95.5268
-91.3618
-104.085
-105.985
-87.8509
-87.8155
-89.7754
-93.1103
-102.651
-98.416
-99.2531
-91.1482
-87.3075
-105.811
-84.2757
-86.9602
-92.4733
-106.128
-100.221
-98.3607

CS
-102.001
-102.266
-98.412
-121.486
-107.264
-87.7452
-107.431
-104.763
-96.7127
-106.11
-108.464
-112.91
-103.245
-92.7187
-119.641
-106.905
-100.191
-106.617
-107.747
-103.777
-96.9107

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ICL
-80.3044
-90.2236
-95.9246
-79.49
-97.866
-83.2031
-83.9429
-83.3807
-89.8237
-107.754
-77.4452
-103.73
-84.0796
-76.6763
-104.233
-86.3906
-88.5964
-92.0656
-98.1041
-94.0206
-95.8372

PS
-93.8873
-96.1141
-92.8452
-104.77
-107.809
-81.7279
-92.1318
-102.515
-94.769
-105.176
-101.052
-102.55
-99.8701
-94.6158
-113.14
-88.5355
-96.097
-96.0399
-96.6352
-99.578
-97.0165

InhA
-88.9512
-90.8165
-97.7398
-96.3855
-108.76
-77.141
-93.5277
-86.9096
-90.8683
-105.706
-101.227
-106.509
-89.7596
-86.0126
-112.809
-84.0621
-93.0566
-91.5438
-92.3131
-95.0073
-92.9122

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KR22
KR23
KR24
KR25
KR26
KR27
KR28
KR29
KR30
KR31
KR32
KR33
KR34
KR35

2,4-diClC6H3
2-FC6H4
3-FC6H4
4-FC6H4
2,4-diFC6H3
Furan-2yl
Thiophen-3-yl
Pyrrol-2yl
Pyridin-2-yl
Pyridin-3-yl
Pyridin-4-yl
Naphthalen-2-yl
Naphthalen-3-yl
Anthracen-9-yl

World Journal of Pharmacy and Pharmaceutical Sciences

-101.99
-91.9026
-103.691
-89.8776
-94.7923
-80.5848
-70.6235
-94.0145
-92.5894
-115.934
-106.128
-108.057
-103.691
-119.898

-111.343
-109.302
-82.9469
-106.571
-109.934
-90.4753
-78.8087
-106.499
-98.6213
-121.365
-107.747
-142.08
-82.9469
-115.102

-90.6852
-104.428
-95.449
-73.136
-95.8531
-77.8077
-78.2365
-82.1012
-83.8498
-88.8189
-98.1041
-94.6875
-95.449
-59.2644

-94.8492
-99.0724
-94.7426
-93.6172
-93.9541
-83.3594
-84.5833
-95.8456
-91.1919
-105.357
-96.6352
-112.943
-94.7426
-116.648

-97.7461
-102.379
-89.9811
-99.2324
-101.941
-77.212
-84.6069
-95.599
-89.5359
-108.92
-92.3131
-120.054
-89.9811
-104.342

Table 4: Pyridine-chalcone conjugates (KR1-KR35) with their Moldock Scores

(kcal/mol) against selected antitubercular drug targets.

Compound
KR1
KR2
KR3
KR4
KR5
KR6
KR7
KR8
KR9
KR10
KR11
KR12
KR13
KR14
KR15
KR16
KR17
KR18
KR19
KR20
KR21
KR22
KR23

R
Phenyl
2-MeC6H4
3-MeC6H4
4-MeC6H4
2-OMeC6H4
3-OMeC6H4
4-OMeC6H4
3-OHC6H4
4-OHC6H4
3,5-diOHC6H3
4,5-diOHC6H3
2-Me,5-OHC6H3
2-NH2C6H4
3-NH2C6H4
4-NH2C6H4
2-NO2C6H4
3-NO2C6H4
4-NO2C6H4
2-ClC6H4
3-ClC6H4
4-ClC6H4
2,4-diClC6H3
2-FC6H4

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MabA
-88.4086
-94.2264
-102.57
-106.656
-102.526
-74.0527
-82.2662
-104.579
-88.6987
-91.7312
-93.5827
-99.2442
-80.4549
-86.082
-101.91
-99.2442
-79.2065
-98.0939
-103.691
-99.4005
-86.6383
-86.828
-102.644

OAT
-73.5491
-79.9528
-79.5769
-80.1541
-88.2657
-62.7041
-79.5054
-81.8349
-74.6151
-68.6193
-86.4768
-84.4368
-81.2998
-63.5364
-90.8969
-84.4368
-77.1796
-71.2051
-82.9469
-70.7923
-66.7165
-80.1743
-74.3106

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LS
-87.5657
-92.9645
-97.5413
-89.3755
-101.537
-80.0789
-95.6765
-98.3754
-93.9618
-92.1224
-96.8181
-97.531
-92.6002
-82.3916
-107.937
-97.531
-87.2604
-101.304
-95.449
-85.7546
-95.5683
-96.1634
-104.703

QAPRT
-77.8365
-82.2714
-89.6043
-94.9893
-96.6126
-74.8006
-77.2506
-91.8257
-86.4725
-80.0109
-98.3924
-96.2878
-85.956
-76.4916
-99.0164
-96.2878
-80.8184
-90.7012
-94.7426
-88.5613
-81.2432
-88.6799
-99.3127

GLmU
-84.6719
-84.3382
-90.6182
-97.5183
-101.322
-82.5287
-90.506
-90.4049
-83.9321
-83.2349
-86.9817
-102.491
-83.1111
-83.7712
-103.555
-102.491
-88.5372
-91.579
-89.9811
-92.0864
-80.0666
-98.842
-89.327

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KR24
KR25
KR26
KR27
KR28
KR29
KR30
KR31
KR32
KR33
KR34
KR35

3-FC6H4
4-FC6H4
2,4-diFC6H3
Furan-2yl
Thiophen-3-yl
Pyrrol-2yl
Pyridin-2-yl
Pyridin-3-yl
Pyridin-4-yl
Naphthalen-2-yl
Naphthalen-3-yl
Anthracen-9-yl

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-102.192
-101.399
-96.7815
-79.0072
-83.0322
-97.5773
-92.3867
-103.691
-102.644
-94.0367
-110.443
-119.576

-80.8224
-81.2647
-88.4274
-52.7795
-51.8248
-76.8254
-67.8127
-82.9469
-74.3106
-94.8787
-73.1929
-92.136

-97.7032
-96.5202
-95.1317
-76.68
-86.7161
-93.5449
-88.3799
-95.449
-104.703
-109.504
-94.3755
-101.336

-95.2263
-91.8843
-87.8335
-66.4658
-68.7265
-92.0795
-79.477
-94.7426
-99.3127
-99.1087
-104.88
-103.883

-95.4188
-92.8393
-92.4578
-81.1523
-68.4562
-88.709
-92.0832
-89.9811
-89.327
-85.4469
-100.449
-119.645

Molecular docking technique was employed to study the database of compounds pyridinechalcone conjugates KR1-KR35 listed in (Table 3 and 4) for their binding phenomenon
against selected potential antitubercular drug targets using MVD as well as to locate the
interactions between pyridine-chalcone conjugates KR1-KR35 and drug targets. MVD
requires the receptor and ligand coordinates in either Mol2 or PDB format. Non polar
hydrogen atoms were removed from the receptor file and their partial charges were added to
the corresponding carbon atoms. Molecular docking was performed using MolDock docking
engine of Molegro software. The binding site was defined as a spherical region which
encompasses all protein atoms within 15.0 Ao of bound crystallographic ligand with respect
to the individual target protein. The dimensions are showed in the atom X, Y and Z axes, as
seen in case individual targets such as SK = X [37.84]; Y [4.71]; Z [13.83], CS= X [54.14]; Y
[8.71]; Z [19.83], ICL = X [19.50]; Y [41.06]; Z [53.00], PS = X [33.65]; Y [33.50]; Z
[43.74], Inh A = X [-16.30]; Y [-35.37]; Z [16.93], MabA = X [1.06]; Y [15.38]; Z [16.89],
OAT= X [37.84]; Y [4.71]; Z [13.83], LS = X [-17.53]; Y [10.22]; Z [-25.15], QAPRT = X [14.63]; Y [44.13]; Z [17.74] and Glm U = X [29.15]; Y [-30.97]; Z [37.01], respectively.
Default settings were used for all the calculations. Molecular docking was performed using a
grid resolution of 0.3 Ao and for each of the 10 independent runs; a maximum number of
1500 iterations were executed on a single population of 50 individuals (Figure 1 and 2).

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Table 5: Summarized molecular docking results of Pyridine-Chalcone conjugates (KR1KR35) against selected antitubercular drug targets.
Moldock
Score
(kcal/mol)
-119.898
-142.08

Target
Code

PDB
ID

Best Fit
Ligand

R Group
Substituent

SK
CS

1L4Y
2QHF

KR35
KR33

Anthracen-9-yl
Naphthalen -2-yl

ICL

1F8I

KR10

3,5-diOHC6H3

-107.754

13

PS
InhA
MabA
OAT
LS
QAPRT
GLmU

1N2H
2X22
1UZN
3IT4
2C9D
1QPN
3D8V

KR35
KR33
KR35
KR33
KR33
KR34
KR35

Anthracen-9-yl
Naphthalen -2-yl
Anthracen-9-yl
Naphthalen -2-yl
Naphthalen -2-yl
Naphthalen-3-yl
Anthracen-9-yl

-116.648
-120.054
-119.576
-94.8787
-109.504
-104.88
-119.645

1
1
2
5
6
2
6

No. of
H-bond Interacting
H-Bonds Residues
7
10

Thr 17, Gly 12, Gly 14, Lys 15

Arg 49, Ser 137, Ser 10
Ser 317, Ser 191, Glu 285, Asp
153, Ser 91, Trp 93, Gly 92
Val 187
Val 187
Gly 90
Lys 189, Thr 127
Gly 85, Thr 87, Phe 90
Ser 248
Ser 112, Gly 15, Ala 14

.
Figure 1: a) Active binding site, binding mode and H-bond interactions of KR35 against
SK b) Active binding site, binding mode and H-bond interactions of KR33 against CS c)
Active binding site, binding mode and H-bond interactions of KR10 against ICL d)
Active binding site, binding mode and H-bond interactions of KR35 against PS e) Active
binding site, binding mode and H-bond interactions of KR33 against InhA.

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Figure 2: a) Active binding site, binding mode and H-bond interactions of KR35 against
MabA b) Active binding site, binding mode and H-bond interactions of KR33 against
OAT c) Active binding site, binding mode and H-bond interactions of KR33 against LS
d) Active binding site, binding mode and H-bond interactions of KR34 against QAPRT
e) Active binding site, binding mode and H-bond interactions of KR35 against Glmu.
3. RESULTS AND DISCUSSION
Molecular docking approach has been used as an essential means in facilitating drug-target
search. The compound with least binding energy against each target protein is considered as
Best fit. By this means, it is possible to understand how the compounds interact with the
receptor. The results emerging out of this study can be used to establish the possible inherent
mechanism of action of pyridine-chalcone conjugates KR1-KR35 as potential antitubercular
agents. The Molecular docking simulation technique was performed using MVD program
with 35 designed compounds assumed to be having antitubercular activity. Each compound
was docked into 10 different targets shown in Table 3 and 4. The lowest energy docked
conformation of the most populated cluster (the best cluster) was selected and then taken into
account. Table 5 summarizes the result of the docking interactions of the selected compounds

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against each target. From the results, KR35 was accomplished best binding efficiency against
SK, PS, MabA and GLmU with Moldock scores -119.898, -116.648, -119.576 and -119.645
kcal/mol respectively. Similarly, compound KR33 against CS, InhA, OAT and LS with
Moldock scores -142.08, -120.054, -94.8787 and -109.504 kcal/mol respectively.
Correspondingly compound KR10 and KR34 showed good binding efficiency against the
remaining two targets ICL and QAPRT with Moldock scores -107.754 and -104.88 kcal/mol
respectively. Among 35 molecules belongs to 1,3,5-triaizine-Chalcone basic scaffold the
best fit molecule showed a good binding efficiency against each protein target is identified
on the basis of their Moldock scores (kcal/mol). The results are used to understand the status
of binding capacity of this class of molecules assumed to be having antitubercular activity
with established mechanism of action. However for strengthen this approach our studies
carried forward by examining the binding orientation and H-bond interacting residues of the
best scored molecule and co-crystallized ligand of active binding site region of individual
protein target selected for Molecular docking methodology (Figure 1 and 2).
Molecular docking studies on a series of pyridine-chalcone conjugates (KR1-KR35) against
1L4Y showed that KR35 scored least binding energy with 7 hydrogen bond interactions and
the corresponding interacting residues are Thr 17, Gly 12, Gly 14, Lys 15, these hydrogen
bonds not only relevant for the binding KR35 to 1L4Y to exhibit highly selective and potent
binding affinity. The residues that participate in H-bond interactions with KR35 are may
contribute for further improvement of the binding efficiency. Similarly, pyridine-chalcone
conjugates (KR1-KR35) against 2QHF showed that KR33 scored least binding energy with
10 hydrogen bond interactions and the corresponding interacting residues are Arg 49, Ser
137, Ser 10 these hydrogen bonds not only relevant for the binding KR33 to 2QHF to exhibit
highly selective and potent binding affinity. The residues that participate in H-bond
interactions with KR33 are may contribute for further improvement of the binding efficiency.
Similarly, pyridine-chalcone conjugates (KR1-KR35) against 1F8I showed that KR10 scored
least binding energy with 13 hydrogen bond interactions and the corresponding interacting
residues are Ser 317, Ser 191, Glu 285, Asp 153, Ser 91, Trp 93, Gly 92 these hydrogen
bonds not only relevant for the binding KR10 to 1F8I to exhibit highly selective and potent
binding affinity. The residues that participate in H-bond interactions with KR10 are may
contribute for further improvement of the binding efficiency. Similarly, pyridine-chalcone
conjugates (KR1-KR35) against 1N2H showed that KR35 scored least binding energy with 1
hydrogen bond interaction and the corresponding interacting residue is Val 187 this hydrogen

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bond not only relevant for the binding KR35 to 1N2H to exhibit highly selective and potent
binding affinity. The residue that participates in H-bond interaction with KR35 may
contribute for further improvement of the binding efficiency. Similarly, pyridine-chalcone
conjugates (KR1-KR35) against 2X22 showed that KR33 scored least binding energy with 1
hydrogen bond interaction and the corresponding interacting residue is Val 187 this hydrogen
bond not only relevant for the binding KR33 to 2X22 to exhibit highly selective and potent
binding affinity. The residue that participates in H-bond interaction with KR33 may
contribute for further improvement of the binding efficiency. Similarly, pyridine-chalcone
conjugates (KR1-KR35) against 1UZN showed that KR35 scored least binding energy with 2
hydrogen bond interactions and the corresponding interacting residue is Gly 90 these
hydrogen bonds not only relevant for the binding KR35 to 1UZN to exhibit highly selective
and potent binding affinity. The residue that participates in H-bond interactions with KR35
may contribute for further improvement of the binding efficiency. Similarly, pyridinechalcone conjugates (KR1-KR35) against 3IT4 showed that KR33 scored least binding
energy with 5 hydrogen bond interactions and the corresponding interacting residues are Lys
189, Thr 127 these hydrogen bonds not only relevant for the binding KR33 to 3IT4 to exhibit
highly selective and potent binding affinity. The residues that participate in H-bond
interactions with KR33 are may contribute for further improvement of the binding efficiency.
Similarly, pyridine-chalcone conjugates (KR1-KR35) against 2C9D showed that KR33
scored least binding energy with 6 hydrogen bond interactions and the corresponding
interacting residues are Gly 85, Thr 87, Phe 90 these hydrogen bonds not only relevant for
the binding KR33 to 2C9D to exhibit highly selective and potent binding affinity. The
residues that participate in H-bond interactions with KR33 are may contribute for further
improvement of the binding efficiency. Similarly, pyridine-chalcone conjugates (KR1-KR35)
against 1QPN showed that KR34 scored least binding energy with 2 hydrogen bond
interactions and the corresponding interacting residue is Ser 248 these hydrogen bonds not
only relevant for the binding KR34 to 1QPN to exhibit highly selective and potent binding
affinity. The residue that participates in H-bond interactions with KR34 may contribute for
further improvement of the binding efficiency. Similarly, pyridine-chalcone conjugates
(KR1-KR35) against 3D8V showed that KR35 scored least binding energy with 6 hydrogen
bond interactions and the corresponding interacting residues are Ser 112, Gly 15, Ala 14
these hydrogen bonds not only relevant for the binding KR35 to 3D8V to exhibit highly
selective and potent binding affinity. The residues that participate in H-bond interactions with
KR35 are may contribute for further improvement of the binding efficiency (Figure 1 and 2).

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4. CONCLUSIONS
This article presents molecular docking technique currently applied to database of
compounds assumed to be potential antitubercular drugs with pre-defined biological targets.
In summary, we could hypothesize KR35 as a potential modulator of SK, PS, MabA and
GlmU, similarly KR33 against CS, InhA, OAT and LS, KR10 and KR34 against the
remaining two targets ICL and QAPRT respectively.
ACKNOWLEDGMENTS
One of the authors Asst. Prof. A. Kanakaraju is thankful to Dr. Rene Thomsen, M/S Molegro
Aps, Denmark for providing academic software (one month trail license) to Andhra
University during the course of our research work.
CONFLICTS OF INTEREST
We declare that, we all authors have no conflict of interest.
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