Synthesis, characterization and molecular docking of novel quinoline and pyridine derivatives

Article abstract of DOI:10.13005/ojc/330604

A new series of substituted quinoline and pyridine derivatives 6a-h are synthesized by the coupling of hydrazide derivatives 4a-b with substituted carboxylic acids 5a-c in the presence of N,N,N’,N’-tetramethyl-o-(benzotriazol-1-yl) uranium tetrafluoroborate TBTU as a coupling agent and lutidine as a base. The newly synthesized compounds 6a–l is characterized by analytical NMR and mass spectral data. The newly synthesized compounds were subjected to molecular docking studies for the inhibition of human Aurora A kinase target to evaluate their potential value for the treatment of cancers.

Full text of DOI:10.13005/ojc/330604

ISSN: 0970-020 X
CODEN: OJCHEG
017, Vol. 33, No.(6):
Pg. 2713-2719
ORIENTAL JOURNAL OF CHEMISTRY
An International Open Free Access, Peer Reviewed Research Journal
2
www.orientjchem.org
Synthesis, Characterization and Molecular Docking of Novel
Quinoline and Pyridine Derivatives
1
2
3
4
SUHEB SALEH , USAMA AL-TIMARI , AEED AL- FAHDAWI , NASSEEM EL-KHATATNEH ,
5
4
6,
CHANDRA , MAHENDRA M and MOHAMMED AL-GHORBANI *
1
Department of Chemistry, Al Rasafi School, Ministry of Education , Anbar, Iraq.
2
Department of Chemistry, College of Health Medical Technology, Baghdad, Iraq.
Department of Chemistry, College of Education for Women , University of Anbar, Iraq.
Department of Studies in Physics, Manasagangotri, University of Mysore, Mysore-570006,
Karnataka, India.
3
4
5
Department of Physics, The National Institute of Engineering (NIE), Mysore-570008, Karnataka, India.
6
Department of Chemistry, College of Education, University of Thamar, Yemen.
*
Corresponding author E-mail: malghorbani@yahoo.com
http://dx.doi.org/10.13005/ojc/330604
(Received: August 01, 2017; Accepted: August 25, 2017)
ABSTRACT
A new series of substituted quinoline and pyridine derivatives 6a-h are synthesized by the
coupling of hydrazide derivatives 4a-b with substituted carboxylic acids 5a-c in the presence of
N,N,N’,N’-tetramethyl-o-(benzotriazol-1-yl) uranium tetrafluoroborate TBTU as a coupling agent
and lutidine as a base. The newly synthesized compounds 6a–l is characterized by analytical
NMR and mass spectral data. The newly synthesized compounds were subjected to molecular
docking studies for the inhibition of human Aurora A kinase target to evaluate their potential value
for the treatment of cancers.
Keyword: Synthesis, Molecular docking, Quinoline, Pyridine, NMR and Mass spectral.
INTRODUCTION
been shown to possess useful biological activities,
4
5-8
9
such as antiprion , antimicrobial , antibacterial ,
1
0- 12
13-15
Quinoline nucleus represent a significant
antitubercular
and anticancer activities
.
class of heterocycles, they occur in various natural
products, especially in alkaloids and exhibit
exceptionally broad spectrum of biological
Similarly, it is well documented that pyridine nucleus
is associated with a variety of pharmacological
actions, including, pathogenesis of cancer, HIV,
1
-3
16,17
activities . The synthesis of quinoline and their
derivatives has attracted considerable attention
from organic and medicinal chemists for many years
as a large number of natural and synthetic products
autoimmune and inflammatory diseases.
In view of the interest in the activity
spectrum and profile of quinoline and pyridine, and
in continuation of our work on the synthesis of new
compounds of pharmacological and biological
4
–8
contain this heterocyclic nucleus . Some
derivatives containing quinoline ring system have

2
714
GHORBANI et al., Orient. J. Chem., Vol. 33(6), 2713-2719 (2017)
1
8-22
interest , we describe herein the preparation and (5-Methyl-pyridin-2-yloxy)-acetic acid ethyl ester (3b)
−
1
Doking study of some new quinoline and pyridine
derivatives (6a-h).
Yield 87ꢀ, yellow liquid, IR (cm ): 1745
1
(C=O); 3110-3215 (NHNH ) H NMR (CDCl ): δ
2
3
(
ppm) = 2.27 (t, 3H, CH ), 2.45 (t, 3H, CH ), 3.22
3
3
MATERIAL AN METHODS
(q, 2H, CH ), 4.29 (t, 2H, OCH ), 7.27-8.74 (m, 3H,
2
2
Ar-H). LC-MS m/z =196 Anal. Cal. for C H NO : C,
10
13
3
General methods
61.53; H, 6.71. Found: C, 61.38; H, 6.54ꢀ.
Chemicals were purchased from Sigma
Aldrich Chemical Co. TLC was performed on General synthesis of hydrazide derivatives (4a-b)
aluminium-backed silica plates and visualized by Hydrazine hydrate (0.018 mol) was added
UV-light. Melting points were determined on a to a solution of compounds 3a-b (0.018moL) in
Thomas Hoover capillary melting point apparatus absolute ethanol (30 mL) and continuously stirred
with a digital thermometer. IR spectra were for 2-4 h. at room temperature. A solid was separated
determined on JASCO FT-IR 4000 spectro-
photometers. NMR spectra were recorded on
Agilent-400 NMR MHz spectrometer in CDCl3.
out, which was quenched with water (50 mL), filtered
and washed with water (50 mL). Finally, the solid
was dried under vacuum and recrystallized with
ethanol to obtain compounds 4a-b.
Chemical shifts were recorded in parts per million
downfield from tetramethylsilane. Mass spectra
were carried out on LC-MS/MS (API-4000) mass
spectrometer. The elemental analysis of the
(
Quinolin-8-yloxy)-acetic acid hydrazide (4a)
o
Yield 80ꢀ, white solid mp; 145-147 C, IR
−1
1
compounds was performed on a Perkin Elmer 2400 (cm ): 1720 (C=O); H NMR (CDCl ): δ (ppm) = 4.45
3
Elemental Analyzer. The results of elemental (s, 2H, NH ), 4.71 (s, 2H, CH ), 7.21-8.87 (m, 6H,
2
2
analyses were within ±0.4ꢀ of the theoretical Ar), 9.41 (s, 1H, NH), LC-MS m/z =182 Anal. Cal. for
values.
C H N O : C, 53.03; H, 6.12. Found: C, 52.86;
8 11 3 2
H, 6.03ꢀ.
Chemical synthesis
General synthesis of ethyl acetate analogues (3a-b) (5-Methyl-pyridin-2-yloxy)-acetic acidhydrazide (4b)
o
A mixture of commercially available
Yield 87ꢀ, white solid mp; 178-180 C, IR
−
1
1
8
-hydroxy quinoline or 5-methyl-pyridin-2-ol 1a-b (cm ): 1735(C=O); H NMR (CDCl ): δ (ppm) =4.23
3
(
0.03 mol) and chloroethyl acetate 2 (0.045 mol) in (s, 2H, NH ), 4.83 (s, 2H, CH ), 7.55-8.37 (m, 3H,
2
2
dry acetone (30 mL) with anhydrous potassium Ar), 9.21 (s, 1H, NH); LC-MS m/z =218 Anal. Cal. for
carbonate (0.045 mol) were refluxed for 10-16 C H N O : C, 60.82; H, 5.10. Found: C, 60.60; H,
11
11
3
2
hours.The reaction mixture was cooled and solvent 5.02ꢀ.
removed by distillation. The residual mass was
General synthesis of compounds (6a-h)
triturated with cold water to remove potassium
carbonate, and extracted with ether (3×30 mL).The
ether layer was washed with 10ꢀ sodium hydroxide
solution (3×30 mL) followed by water (3×30 mL)
and then dried over anhydrous sodium sulphate
and evaporated to afford compounds 3a-c. The
physical and analytical data of the synthesized title
compounds 3a-c are given as follows.
Hydrazide derivatives (4a-b, 3 mmol) in
o
dry DCM (20 ml) was stirred at 25–30 C, and then
lutidine (4 mmol) was added, followed by the addition
of substituted amino-4-phenyl-1,3-thiazoles
(
3 mmol). The reaction mixture was stirred at the
o
same temperature for 30 min. then cooled to 0–5 C
and TBTU (3 mmol) was added over a period of 30
o
min maintaining the temperature below 5 C. The
reaction mass was stirred overnight and monitored
by TLC using chloroform: methanol (9:1) as the
mobile phase. The solvent was evaporated at
reduced pressure, quenched by the addition of
crushed ice and the obtained solid was filtered, dried
and recrystallized from ethanol to afford compounds
4
-(Quinolin-8-yloxy)-acetic acid ethyl ester (3a)
−
1
Yield 90ꢀ, yellow liquid, IR (cm ): 1735
1
(
(
(
C=O), 3115-3225 (NHNH ); H NMR (CDCl ):δ
ppm) = 2.36 (t, 3H, CH ), 3.28 (q, 2H, CH ), 4.21
t, 2H, OCH ), 7.18-8.85 (m, 6H, Ar-H). LC-MS m/z
2
3
3
2
2
=
232 Anal. Cal. for C H NO :C, 67.52; H, 5.67.
13 13 3
6a-h in good yield.
Found: C, 67.35; H, 5.51ꢀ.

GHORBANI et al., Orient. J. Chem., Vol. 33(6), 2713-2719 (2017)
2715
(
4-Fluoro-phenyl)-acetic acid N’-[2-(quinolin-8-
yloxy)-acetyl]-hydrazide (6a)
Yield 76ꢀ, white solid mp; 255-257 C, IR
cm ) 1640, 1675 (C=O), 3245–3470 (NH–NH);
NMR (CDCl ): δ (ppm) = 1.93 (s, 3H, CH ), 3.51
3
3
(s, 2H, CH ), 4.68 (s, 2H, CH ), 6.28-7.65 (m, 7H,
2
2
o
Ar), 10.32 (d, 2H, 2NH). LC-MS m/z = 334 Anal. Cal.
for C H ClN O : C, 57.58; H, 4.83. Found: C, 57.67;
−
1
(
16
16
3
3
1
H NMR (CDCl ): δ (ppm) = 3.21 (s, 2H, CH ), 4.76
3
2
H, 4.35ꢀ.
(
s, 2H, CH ), 7.26-8.94 (m, 10H, Ar), 10.23 (d, 2H,
2
2
NH); LC-MS m/z =354 Anal. Cal. for C H FN O :
19 16 3 3
(3,4-Dichloro-phenyl)-acetic acid N’-[2-(5-methyl-
pyridin-2-yloxy)-acetyl]-hydrazide (6g)
C, 64.58; H, 4.56. Found: C, 64.37; H, 4.80ꢀ.
o
Yield 68ꢀ, white solid mp; 286-288 C, IR
cm ): 1645, 1690 (C=O), 3230–3455 (NH–NH);
(
4-Chloro-phenyl)-acetic acid N’-[2-(quinolin-8-
yloxy)-acetyl]-hydrazide (6b)
Yield 80 ꢀ, white solid, mp; 258-260 C,
−1
(
1
H NMR (CDCl ): δ (ppm) = 1.98 (s, 3H, CH ), 3.47
3
3
o
(
s, 2H, CH ), 4.50 (s, 2H, CH ), 6.27-7.55 (m, 6H,
2
2
−
1
IR (cm ): 1630, 1685 (C=O), 3255–3475 (NH–NH);
13
Ar), 10.20 (d, 2H, 2NH). C NMR (100MHz, CDCl ):
3
1
H NMR (CDCl ): δ (ppm) = 3.44 (s, 2H, CH ), 4.83
3
2
34.4, 54.19, 126.24, 133.49, 136.74, 137.65,
138.87, 143.36, 164.15. LC-MS m/z = 368 Anal.
Cal. for C H Cl N O : C, 52.19; H, 4.11. Found: C,
(
s, 2H, CH ), 7.21-8.85 (m, 10H, Ar), 10.24 (d, 2H,
2
2NH), LC-MS m/z =370 Anal. Cal. for C H ClN O :
19 16 3 3
16
15
2
3
3
C, 61.71; H, 4.36. Found: C, 61.66; H, 4.17ꢀ.
52.23; H, 4.06ꢀ.
(
8
3,4-Dichloro-phenyl)-acetic acid N’-[2-(quinolin-
-yloxy)-acetyl]-hydrazide (6c)
Yield 73ꢀ, white solid mp; 228-230 C, IR
4
2
-Methoxy-benzoic acid N’-[2-(5-methyl-pyridin-
-yloxy)-acetyl]-hydrazide (6h)
o
o
Yield 64ꢀ, white solid mp; 274-276 C, IR
−
1
(
cm ): 1660, 1690 (C=O), 3235–3455 (NH–NH);
−1
(
cm ): 1625, 1675 (C=O), 3240–3460 (NH–NH);
1
H NMR (CDCl ): δ (ppm) = 3.35 (s, 2H, CH ), 4.69
s, 2H, CH ), 7.43-8.97 (m, 9H, Ar), 10.21 (d, 2H,
3
2
1
H NMR (CDCl ): δ (ppm) = 2.08 (s, 3H, CH ), 3.24
3
3
(
2
(s, 3H, CH ), 4.47 (s, 2H, CH ), 6.33-7.70 (m, 7H,
3
2
2
NH). LC-MS m/z =405 Anal. Cal. for
Ar), 10.28 (d, 2H, 2NH). LC-MS m/z = 316 Anal. Cal.
for C H N O : C, 60.94; H, 5.43. Found: C, 61.01;
H, 5.32ꢀ.
C H Cl N O : C, 56.45; H, 3.74. Found: C, 56.32;
H, 3.51ꢀ.
19
15
2
3
3
16 17
3
4
4
-Methoxy-benzoic acid N’-[2-(quinolin-8-yloxy)-
RESULT AND DISCUSSION
acetyl]-hydrazide (6d)
o
Yield 78ꢀ, white solid mp; 253-255 C, IR
−
1
1
Synthesis of the target compounds 6a-h
was performed according to the reactions illustrated
in scheme 1. Initially, esterification of 8-hydroxy
quinoline and 5-methyl-pyridin-2-ol 1a-b was
performed by using chloroethyl acetate 2 in the
presence of anhydrous potassium carbonate and
dry acetone at reflux temperature to afford
compounds 3a-b.These materials were stirred with
hydrazine hydrate in ethanol to afford hydrazide
derivatives 4a-b. Finally, the target derivatives 6a-
h were obtained in good yields by stirring of
compounds 4a-b with substituted carboxylic acids
a-c in the presence of N,N,N’,N’-tetramethyl-o-
benzotriazol-1-yl) uranium tetrafluoroborate
(TBTU) as a coupling agent and lutidine as a base
in dry DCM at RT. The structure elucidations of the
synthesized compounds were confirmed by IR,
NMR, mass spectrometry and elemental analysis.
(
cm ):1635, 1680 (C=O), 3230–3470 (NH–NH); H
NMR (CDCl ): δ (ppm) = 3.30 (s, 3H, CH ), 4.88
3
3
(
s, 2H, CH ), 7.37-8.74 (m, 10H, Ar), 10.27-10.34
2
(
d, 2H, 2NH). LC-MS m/z = 352 Anal. Cal. for
C H N O : C, 64.95; H, 4.88. Found: C, 64.81;
H, 4.67ꢀ.
19
17
3
4
(
4-Fluoro-phenyl)-acetic acid N’-[2-(5-methyl-
pyridin-2-yloxy)-acetyl]-hydrazide (6e)
o
Yield 71ꢀ, white solid mp; 211-213 C, IR
−
1
1
(
cm ):1640, 1695 (C=O), 3250–3475 (NH–NH); H
NMR (CDCl ): δ (ppm) = 1.89 (s, 3H, CH ), 3.34
s, 2H, CH ), 4.41 (s, 2H, CH ), 6.18-7.69 (m, 7H,
Ar), 10.13 (d, 2H, 2NH). LC-MS m/z = 318 Anal.
Cal. for C H FN O : C, 60.56; H, 5.08. Found: C,
3
3
5
(
2
2
16
16
3
3
60.45; H, 5.04ꢀ.
(
4-Chloro-phenyl)-acetic acid N’-[2-(5-methyl-
pyridin-2-yloxy)-acetyl]-hydrazide (6f)
o
Yield 65ꢀ, white solid mp; 282-284 C, IR
cm ): 1635,1685(C=O), 3240–3460 (NH–NH); H
The spectra of the title compound 4a were
considered as a representative example of the
−
1
1
(

2
716
GHORBANI et al., Orient. J. Chem., Vol. 33(6), 2713-2719 (2017)
series 4a-b. In IR spectra, the compound 4a showed indicate the formation of compound 6a. The mass
-
1
band at 1720 and in between 3115-3225 cm
+
spectra of compound 6a gave significant stable (M )
corresponding to carbonyl and NH-NH stretching
frequencies respectively. In H NMR spectra of
2
peak at m/z 354. Further, all the target compounds
1
13
6a-h were clearly confirmed by C NMR.
compound 4a showed one singlet at d 4.45
assigned to NH2 and broad singlet at d 4.71 Molecular docking studies
assigned to OCH protons, it also revealed broad
The molecular docking was performed and
2
singlet at d 9.41 assigned to amide proton as well analyzed using Auto Dock 4.2. A Lamarkian genetic
as multiplet signals appeared in the range d 7.21- algorithm method implemented in the program suite
8.87 for aromatic protons.
was employed to identify appropriate binding modes
and conformation of the ligand molecules. Gasteiger
In IR spectra of compounds 6a was charges were added and the rotatable bonds were
confirmed by the appearance of one more carbonyl set by the Auto Dock tools and all torsions were
-
1
at 1685 cm and disappearance of the NH
allowed to rotate.Polar hydrogen atoms were added
and Kollaman charges were assigned to the protein
using Auto Dock tools (ADT). All the compounds
2
1
absorption peak. In addition, H NMR spectra
showed disappearance of NH protons at 4.45 and
2
(6a-h) were found to have minimum binding energy
an increase in one more NH proton and four
aromatic protons with earlier aromatic proton peaks
at d10.23 and 7.26-8.94 respectively, which clearly
ranging from -6.29 to -8.20 kJ/mol with Aurora A
kinase (PDB Code:3FDN).
O
Anhyd. K CO3
NH NH H O
2
O
2
2.
2
Ar-OH + Cl
a-b
ArO
Dry. Acetone
EtOH
O
2
1
O
a-b
3
O
HN
NH
R
O
TBTU, Lutidine
Dry DCM
ArO
+
R
COOH
a-d
HN
a-b
5
NH
2
OAr
4
6a-h
Compound
Ar
N
R
Compound
5e
Ar
R
COOH
COOH
COOH
3
H C
5a
N
F
F
COOH
3
H C
5b
5f
N
N
N
Cl
Cl
Cl
Cl
COOH
Cl
COOH
Cl
H
3
C
5
c
5
g
N
N
COOH
H
3
C
COOH
5d
5h
N
OCH
3
OCH
3
Scheme 1. Synthesis of quinoline and pyridine derivatives (6a-h)

GHORBANI et al., Orient. J. Chem., Vol. 33(6), 2713-2719 (2017)
2717
Table. 1:The dock score results of the different quinoline derivatives with Aurora A kinase target
(PDB Code: 3FDN)
Com-
pounds
Binding
Ligand Inhibition
vdW+H- No. of Bonding
Bond
Length
(Å)
Energy Efficiency Constant bond+dissolve
H-
residues
-
1
(
kJ mol )
energy
bonds
6
6
a
b
-6.96
-0.27
-0.3
7.97
2.15
-7.9
2
-
3FDN:A:ARG137:HH22 1.958
3FDN:A: THR217:HN
1.778
-
-7.73
-9.04
-
6
6
6
6
6
8
c
d
e
f
g
h
-8.2
-0.3
-0.29
-0.27
-0.29
-0.3
978.84
2.51
24.63
12.98
4.36
-9.12
-8.99
-6.93
-8.25
-8.48
-7.99
1
-
1
1
1
2
3FDN:A: LYS162:HZ3
-
3FDN:A: LYS162:HZ3
3FDN:A: LYS162:HZ3
3FDN:A: ALA213:HN
2.155
-
1.778
2.171
1.884
-7.64
-6.29
-6.67
-7.31
-6.63
-0.29
13.9
3FDN:A:ARG137:HH22 2.052
FDN:A: ALA213:HN 1.859
3
Enfolding of molecule 6b in the active site pocket
of Aurora Kinase
H-bond interaction of ligand molecule 6a with
3FDN
Enfolding of molecule 6d in the active site pocket of
Aurora Kinase
H-bond interaction of ligand molecule 6c with
3FDN

2
718
GHORBANI et al., Orient. J. Chem., Vol. 33(6), 2713-2719 (2017)
Enfolding of molecule 6g in the active site pocket
of Aurora Kinase
H-bond interaction of ligand molecule 6g with
3FDN
Enfolding of molecules 8h in the active site pocket
of Aurora Kinase
H-bond interaction of ligand molecule 8h with
3FDN
Fig.1 & Fig.2
Among the molecules tested for docking 213 and at a distance of (1.958 and 1.778), (2.155)
study, (3,4-Dichloro-phenyl)-acetic acid N’-[2- and (1.884) Å, respectively (Fig. 2).The docking
(
quinolin-8-yloxy)-acetyl]-hydrazide (6c) showed study results showed that the molecules (6a-h) have
minimum binding energy of -8.20 kJ/mol with ligand good inhibition constant, vdW + H bond + dissolve
efficiency of -0.30. Most of the residues, in nature. in energy with best RMSD value.The details of docked
close proximity to the inhibitor are hydrophobic in score results of the molecules with Aurora A kinase
nature. The ligand molecules, 6b, 6d and 6g (PDB Code:3FDN) are given in the Table 1 (see
revealed binding energy of -7.73, -7.64 and -7.31 supplementary material).
kJ/mol, with ligand efficiency of -0.30, -0.29 and
-
0.30, respectively. These molecules were
ACKNOWLEDGEMENTS
completely wrapped by active site amino acid
residues at the active site pocket region (Fig. 1).
The acknowledgement should be brief and
Similarly, molecules 6a, 6c and 6g were found to must be written about the original supporters of the
show hydrogen bond interaction with active site work and to the reputed institutions.
amino acid residues Arg 137, Thr 217, Lys 162, Ala
REFERENCES
1.
Embrey, M.W.;Wai, J.S.;Funk,T.W.;Homnick,
C.F.; Perlow, D.S.; Young, S.D.; Vacca, J.P.;
Hazuda, D.J.; Felock, P.J.; Stillmock, K.A.;
Witmer, M.V.; Moyer, G.; Schleif, W.A.;
Gabryelski, L.J.;Jin, L.; Chen, IWu.;Ellis, J.D.;
Wong, B.K.;Lin, J.H.;Leonard,Y.M.;Tsou N.N.;

GHORBANI et al., Orient. J. Chem., Vol. 33(6), 2713-2719 (2017)
2719
Zhuang, L. Bioorg. Med. Chem. Lett. 2005,
5, 4550-4554.
V.;Prakash, P.B.;Sarbjit, S.J.;Sukhraj K, Prati,
P. S.; Rahul, J. Biorg Med. Chem. 2004, 12,
6465-6472.
Tseng, C.H.; Chen, Y.L.; Lu, P.J.; Yang, C.N.;
Tzeng, C.C. Bioorg Med Chem. 2008, 16,
3153-3162.
Katarzyna, S.; Lukasz, K.S. Wojciech, S.J.;
Joanna, W.; Marta, S.; Wanda, P.C. Exper.
Therp. 2007, 61, 41-200.
1
2.
Zhuang, L.; Wai, J.S.; Embrey, M.W.; Fisher,
T.E.;Egbertson, M.S.;Payne, L.S Guare, J.P.;
Vacca, J.P.; Hazuda, D.J.; Felock, P.J.;Wolfe,
A.L.; Stillmock, K.A.;Witmer, M.V.; Moyer, G.;
Schleif, W.A.; Gabryelski, L.J.; Leonard,Y.M.;
Lynch, J.J.; Michelson, S.R.; Young, S.D. J.
Med. Chem. 2003, 46, 453-456.
13.
14.
3
.
Atanasova, M.; Ilieva, S.; Galabov, B. Euro. J.
Med. Chem. 2007, 42, 1184-1192.
Cope H, Mutter R, Heal W, Pascoe C, Brown
P, Pratt S, Chen. B. Eur J Med Chem. 2006,
15.
16.
17.
18.
Zhao, Y.L.; Chen, Y.L.; Chang, F.S.; Tzeng,
C.C.; Eur J Med Chem. 2005, 40, 792-797.
Lazennec, G.;Richmond, A.Trends Mol Med.
2010, 16, 133–144.
Schwarz, M.K.; Wells, T.N. Nat Rev Drug
Discov. 2002, 1, 347–358.
4.
41, 1124-1143.
5.
6.
7.
8.
Mamladesai, S.N.; Katagi, M.S.; Khare, P.V.;
Maddi, V.S.;Bhat, A.R.Indian J.Hetero.Chem.
Al-Ghorbani,
M.;
Prabhu,
T.;
2
008, 17, 381-382.
Gurupadaswamy, H.D.;Vigneshwaran, V.;
Prabhakar.B.T.;Khanum, S.A.Bioorg. Chem,
2017, 71, 55-66.
Al-Ghorbani, M.; Prabhu, T.;, Vigneshwaran,
V.; Gurupadaswamy, H.D.; Girish, V.;
Prabhakar, B.T.;Khanum, S.A.Bioorg.Chem,
2016, 65, 73–81.
Al-Ghorbani, M.;Pavankumar, G.S.; Naveen,
P.; Shamanth, H.G, Prabhakar, B.T.;
Shaukath Ara Khanum, Bioorg. Chem, 2016,
65, 110–117.
Kamel, M.A.; Lobna, A.M.; El-Sayed, L.M.;
Mohamed, H.I.; Rania B.H. Biorg Med. Chem.
2
006, 14, 8675-8682.
19.
20.
Ola, E.I.;Sayed, A.; Fatma, E.M.;Shada, E.I.;
Badr, A.A.; Maher, H.E. Indian J. Hetero.
Chem. 2005, 14, 327-330.
Kansagra, B.P.; Bhatt, H.H.; Parikh, A.R.
Indian J. Hetero. Chem. 2000, 10, 05-08.
Santhosh Kumar, S.; Ajay, N.; Tiwari, R.P.;
Praveen. J. Indian J. Chem. 2006, 45, 1734-
9.
1
739.
Amit, N.; Rahul, J. Indian J. Chem. 2008, 47,
17-128.
21.
Al-Ghorbani, M.; Vigneshwaran, V.; Lakshmi
Ranganatha, V.; Prabhakar, B.T.; Khanum,
S.A. Bioorg. Chem, 2015, 60, 136-146.
Al-Ghorbani M, Rekha N.D, Lakshmi
Ranganatha V, Prashanth V, Veer aba
sappagowda T, Khanum S.A, Russian
J. Bioorg. Chem, 2015, 41, 4, 1-8.
1
1
0.
1.
1
Vangapandu, S.; Jain, M.; Jain, R.; Kaur, S.;
Singh, P.P. Bioorg Med Chem. 2004, 12,
22.
2501- 2508.
1
2.
Vikramdeep, M.; Amit, N.; Balasubramanian,