Synthesis, antimicrobial evaluation, and docking studies of some novel benzofuran based analogues of chalcone and 1,4-benzodiazepine

Article abstract of DOI:10.1134/S107036321607029X

A series of novel {5-[4-hydroxy-3-(4-phenyl-2,3-dihydro-1H-benzo[b][1,4]diazepin-2-yl)benzyl]- benzofuran-2-yl}(phenyl)methanones (5a–5g) were prepared by the condensation of (E)-3-{5-[(2- benzoylbenzofuran-5-yl)methyl]-2-hydroxyphenyl}-1-phenylprop-2-en-

Full text of DOI:10.1134/S107036321607029X

ISSN 1070-3632, Russian Journal of General Chemistry, 2016, Vol. 86, No. 7, pp. 1711–1721. © Pleiades Publishing, Ltd., 2016.
Synthesis, Antimicrobial Evaluation, and Docking Studies
of Some Novel Benzofuran Based Analogues
1
of Chalcone and 1,4-Benzodiazepine
a
a*
a
B. Shankar , P. Jalapathi , M. Ramesh ,
a
a
b
A. Kishore Kumar , M. Ragavender , and G. Bharath
a
Department of Chemistry, University College of Science,
Osmania University, Saifabad, Hyderabad, Telangana, 500004 India
e-mail: pochampallij@gmail.com
*
b
Bioengineering and Environmental Sciences, Indian Institute of Chemical Technology, Hyderabad, 500007 India
Received January 23, 2016
Abstract—A series of novel {5-[4-hydroxy-3-(4-phenyl-2,3-dihydro-1H-benzo[b][1,4]diazepin-2-yl)benzyl]-
benzofuran-2-yl}(phenyl)methanones
(5a–5g) were prepared by the condensation of (E)-3-{5-[(2-
benzoylbenzofuran-5-yl)methyl]-2-hydroxyphenyl}-1-phenylprop-2-en-1-one (chalcone) (4a) with various
substituted o-phenylene diamines in the presence of oxalic acid as catalyst. The structures of all compounds
1
13
were characterized by FTIR, H NMR, C NMR, and MS. The representative examples were screened in vitro
for antimicrobial activity. Among all compounds 4g and 5g showed potent antibacterial activity, 4b and 5g
showed good antifungal activity. The data was further compared with structure based investigations using
docking studies with the crystal structure of adenosine-5'-(β,γ-imido)triphosphate (2ONJ) from Staphylococcus
aureus for antibacterial activity and trypsin (1FY5) protein from Fusarium oxysporum for the antifungal
activity. The score values estimated by genetic algorithm were found to have a good correlation with the
experimental inhibitory potencies.
Keywords: chalcones, 1,4-benzodiazepines, oxalic acid, antibacterial, antifungal, docking studies
DOI: 10.1134/S107036321607029X
INTRODUCTION
a number of them have exhibited antihyperglycemic
activity [10]. They were found to be prominent as
antioxidants [11] and anti-inflammatory agents [12].
Tumour inhibiting properties of chalcone are of special
interest and have been found to result from their
effects on malignant cell proliferation through tumour
angiogenesis [13]. Substituted Chalcones have a
preferential reactivity towards thiols in contrast to
amino and hydroxyl groups. Thus, the interactions
with nucleic acids may absent, which can eliminate the
problems of mutagenicity and carcinogenicity common
in various chemotherapeutic [14] activities. Chalcones
are also key precursors in the synthesis of many
biologically important heterocyclic such as 1,4-benzo-
diazepines derivatives.
Design and synthesis of novel types of pharma-
cologically interesting hybrid compounds for drug
discovery have received much attention over past two
decades. Recently, 2-benzylbenzofuran analogous have
been found to possess antitumor activity [1, 2]. A new
series of the substituted 1,4-benzodiazepines obtained
from chalcones is reported in the present work. The
chalcones display wide range of biological activities:
antifungal [3] and antibacterial [4]. In fact, not a lot of
structural templates which can claim an association
with a various range of pharmacological activities such
as cytotoxicity, antiplasmodial and immune suppres-
sion [5] have been reported.
Some of the substituted chalcones have been demon-
strated to posses excellent anticancer [6], antibiotic [7],
antiplasmodial [8] and antiprotozoal properties [9] and
Many biologically active natural products contain a
benzofuran ring as a core unit [15]. Some of the
benzofuran derivatives [16] find the application as pharma-
ceuticals [17], antifungal agents [18], antitumour
agents [19] and antioxidants [20] as antagonists of
1
The text was submitted by the authors in English.
1
711

1
712
SHANKAR et al.
Table 1. Novel chalcones 4a–4g and 1,4-benzodiazepines
a–5g
spectrum showed the presence of absorption bands at
–
1
1
5
1
725 cm due to (2HC=O ) function. H NMR spec-
s
a
trum showed singlet signals at 10.94 and 9.93 ppm,
assigned to phenolic hydroxyl and aldehyde groups,
the signal of up field singlet was assigned to bridge
Comp.
no.
Yield ,
%
R
R
1
R
2
mp, °C
4
a
C
6
H
5
–
–
–
–
–
–
–
–
–
–
–
–
–
–
78
65
75
70
62
65
80
87
85
50
62
72
75
81
95–97
83–85
methylene (–CH –) proton at 3.98 ppm in addition to
2
4
b
3,4-Cl
2
C
6
H
3
the multiple signal of aromatic protons in the region of
7.35–7.45 ppm. The MS of the compound displayed an
4
c
4
-NH
2
2
C
6
H
H
4
4
90–91
+
intense molecular ion peak at m/z 257 [M]
4
d
3-NH
C
6
92–93
corresponding to C H O .
15
12
4
4
e
3-OHC
2,4(OH)
4-BrC
6
H
4
98–100
91–92
Aldehyde 2 was subjected to condense cyclisation
with phenacyl bromide in the presence of potassium
carbonate at the room temperature to obtain the
corresponding 5-[(2-benzoyl benzofuran-5-yl)methyl]-
4
f
2 6 4
C H
4
5
g
a
6
H
4
88–90
C
6
C
6
C
6
C
6
C
6
C
6
C
6
H
H
H
H
H
H
H
5
5
5
5
5
5
5
H
H
H
H
115–118
116–180
120–123
125–127
115–117
105–106
118–120
5
b
CH
Br
3
2
-hydroxybenzaldehyde (3) [1]. The structure of the
product 3 was confirmed on the basis of its spectral
data. The IR spectra showed C=C , HC=O , and –OH
5
c
5
d
Cl
Cl
H
s
s
s
1
–
vibrations in the region of 1650, 1710 and 3550 cm
5
e
NO
2
1
respectively. The H NMR spectrum showed signals of
two singlets which were assigned to aldehyde and
hydroxyl at 9.85 and 10.98 ppm respectively. A signal
of bridged methylene protons appears at 4.00 ppm in
addition to the signal of down field singlet of
benzofuran proton and aromatic protons in the region
of 6.95–8.03 ppm. The structure was further confirmed
5
f
CH
F
3
CH
H
3
5
g
a
Yields of pure isolated compounds.
angiotensin II [21]. In addition to this, a number of
benzofuran derivatives are used in cosmetic formula-
tions [22] and act as brightening agents [23].
1
3
by C NMR. Signals of carbon atoms of the two
carbonyl groups (aldehyde and keto) appeared at
1
,4-Benzodiazepine analogues have attracted our
1
82.54 and 191.8 ppm. Two carbons of the –C–O–C–
attention due to their interesting pharmacological
activities and low toxicity, as many of the guide
molecules utilized for developing potent bio-active
agents possess this fragment as a nucleus. 1,4-Benzo-
diazepine presents an important moiety in several
therapeutic agents, because of its various biological
properties, such as antibacterial [24], antianxiety [25],
antidepressive [26], analgesic [27, 28], antifungal [29],
anthelmintic [30, 31], anti-inflammatory [32] and
anticancer [33, 34] activities. In the present paper we
describe design, synthesis, biological activity testing
and docking studies of the hybrid molecules, contain-
ing both pharmacophore moieties.
linkage in benzofuran nucleus exhibited resonance
peaks at 151.9 and 159.7 ppm, respectively. The
carbon atoms of aromatic ring appeared at 112.7–
1
54.5ppm. The bridged methylene group between two
aromatic rings was observed at 49.0 ppm. MS showed
+
a molecular ion peak at m/z 357.0 [M] , corresponding
to a molecular formula C H O .
2
3
16
4
The resulted compound 3 was allowed to react with
different substituted acetophenones by Claisen
condensation to produce the corresponding substituted
chalcones 4a–4g [36] (Table 1). The IR spectra of
compound 4a revealed strong absorption bands at
–
1
3
440, 1710, and 1688 cm attributed to phenolic
group OH and two C=O groups respectively.
Unsaturated carbons (–CH=CH–) showed a sharp
RESULTS AND DISCUSSION
s
s
–
1
1
Chemistry. For the synthesis of target compounds,
first 5,5'-methylene-bis-salicylaldehyde (2) was prepared
by the reaction of salicylaldehyde (1) with trioxane in
the presence of a mixture of acetic acid and
concentrated sulphuric acid [35]. The structure of bis-
aldehyde 2 was established on the basis of its spectral
intense absorption peak at ν = 1648 cm . Its H NMR
spectra revealed one singlet signal (D O exchangeable)
2
assigned to OH proton in the region of 10.41 ppm.
Two doublets at 6.95 and 8.10 ppm, respectively
confirm presence of aromatic protons. The geometry of
the compound 4a was found to be of trans (E) type as
the value of coupling constant (J) for the two protons
1
properties (IR, H NMR, and MS spectra). The IR
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 7 2016

SYNTHESIS, ANTIMICROBIAL EVALUATION, AND DOCKING STUDIES
1713
Scheme 1. Preparation of chalcones 4a–4g and 1,4-benzodiazepines 5a–5g.
Trioxane,
CHO
OH
OHC
CHO
H SO /AcOH
2
4
o
reflux 90 C,
HO
OH
N -atm 24 h
2
1
2
O
Br
K CO /acetone,
room temperature, 22 h
R1
2
3
R2
RCOCH3
KOH/EtOH,
room temperature
O
HN
CHO
OH
O
N
O
R
O
OH
3
5a−5g
R1
R2
NH2
NH2
Oxalic acid, 20 mol %,
o
DMF, 80 C
O
O
R
O
OH
6a-6g
R = C
H, CH
6
H
5
, 3,4-Cl
2 6 3 2 6 4 2 6 4 6 4 2 6 3 6 4 1 3 2 2
C H , 4-NH C H , 3-NH C H , 3-HOC H , 2,4-(HO) C H , 4-BrC H ; R = H, CH , Br, Cl, NO , F; R =
3
, Cl.
was 15.8 Hz. Singlet peak at 4.01 ppm helped to
confirm the presence of the bridged methylene group
in the final structure. The carbon atoms of the two
carbonyl groups appeared at 184.5 and 192.2 ppm.
Two carbons of the –C–O–C– linkage in benzofuran
ring exhibited peaks at 154.8 and 155.1 ppm, respect-
tively. The bridged methylene group between the two
aromatic rings have been observed at 40.7 ppm.
Carbon atoms of aromatic ring appeared between
oxalic acid at reflux condition to obtain the
corresponding 1,4-benzodiazepines (5a–5g) in good
yields [37]. The structures of all the newly synthesized
1
13
compounds 5a–5g were confirmed by IR, H,
C
NMR, and MS spectra (Table 1). In the IR spectra of
the compound 5a keto C=O , and phenolic group
s
absorption peak appeared at 1710–1795 and
–
1
3498 cm respectively. The absorption peak appeared
–
1
at 3324 cm was attributed to NH group of 1,4-
s
1
12.4–152.4ppm. MS displayed an intense molecular
benzodiazepine. In addition, the absorption bands,
+
ion peak at m/z 459 [M] corresponding to C H O .
corresponding to C=N of the benzodiazepine moiety,
3
1
22
4
s
–
1
were observed at 1609 cm . Thus, the data of IR
spectroscopy supported the formation of the desired
The purified chalcone 4a was condensed with
various substituted o-phenylenediamines in DMF/
1
structure. H NMR spectra contains three broad singlet
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 7 2016

1
714
SHANKAR et al.
Table 2. Antibacterial activity of compounds 4a–4g and 5a–5g
a
b
Zone of inhibition (mm) and MIC (µg/mL) of selected compounds
Gram-negative bacteria
Gram-positive bacteria
Comp. no.
Klebsiella
pneumonia
Pseudomona-
saeruginosa
Bacillus
licheniforms
Bacillus
subtilis
E. Coli
S. aureus
4
4
a
17 (45)
24 (25)
11
20 (79)
16 (50)
14
15 (50)
22 (25)
No activity
16
20 (100)
24 (25)
8
23 (65)
22 (25)
23
20 (70)
55 (75)
9
b
4
c
4
d
13
11
19
18
14
4
e
11
12
08
15
16
19
4
f
No activity
25 (25)
8
No activity
20(25)
15
No activity
25( 50)
18
08
15
No activity
21 (50)
14
4g
5a
5b
24 (25)
9
23 (25)
10
20 (150)
22 (25)
No activity
9
21 (100)
23 (45)
7
22 (50)
No activity (30)
No activity
09
23 (150)
19 (25)
No activity
29
23 (130)
20 (25)
No activity
24
25 (80)
22 (70)
11
5
c
5
d
5
e
10
10
5
f
8
11
18
9
17
20
5
g
26 (25)
26 (25)
24 (45)
24 (25)
No activity
23 (30)
25 (25)
24 (25)
24 (25)
18 (25)
23 (25)
No activity
34 (50)
25 (25)
No activity
Ciprofloxacin
Control (1% DMSO) No activity
No activity No activity
a
b
Zone of inhibition was calculated for stock solution (100 µg/mL). Minimal inhibitory concentration (MIC) values of the particular
compounds are given in brackets. 1% DMSO was used as a control.
at δ = 10.40, 3.95, and 4.01 coresponding to phenolic
bacteria: Bacillus licheniformis, Bacillus subtilis,
Staphylococcus aureus and three gram negative
bacteria: Escherichia coli, Klebsiella pneumonia and
Pseudomonas aeruginosa. Ciprofloxacin was used as
standard drug. Compounds 4a, 4b, 4g, 5b, 5c, and 5g
showed good antibacterial activity against all six
bacterial strains (Table 2). From the screening results
one may conclude that the presence of methyl, chloro
and fluoro groups at 3 position of the phenyl ring
enhance the antibacterial activity. Compounds 4b and
5g showed maximum activity against Staphylococcus
aureus. Compound 4g showed better activity against
B. licheniforms, B. subtilis and P. aeruginosa may be
due to the lipophilic group. Compounds 4c, 5a, 5e, and
5f showed good to moderate antibacterial activity
(>20 mm) against all six bacterial strains. Compounds
4c, 4f, 5c, and 5d showed no activity. It may be
reasoned by the presence of low polar substituents.
group, bridged methylene –CH – and NH group of 1,4-
2
benzodiazepine respectively. For all the synthesized
compounds, aromatic protons appeared at 6.5–
8
.2 ppm. The 1,4-benzodiazepine structure was further
confirmed by the presence of one triplet of benzylic
proton near 3.95 ppm and two doublets of allylic
proton at 1.99 d (1H, J = 12.8 Hz) and 2.02 d (1H, J =
13
1
2.8 Hz). In C NMR spectra signals, corresponded to
the aromatic rings, were observed at 112.9–164.2 ppm.
The keto group signals appeared at 182.3–183.25 ppm
further evidenced to the structures of 1,4-benzo-
diazepines. Benzylic carbon, allylic carbon and
bridged methylene carbon –CH – absorbed at 56.5,
2
4
0.8, and 38.6 ppm respectively. All the synthesized
compounds exhibited satisfactory spectral data
consistent with their molecular structures as shown in
Scheme 1.
Biology. Antimicrobial activity. Antibacterial
activity of the newly synthesized compounds 4a–4g
and 5a–5g were evaluated against three gram positive
Compounds 4a–4g and 5a–5g were also tested
against fungal organisms: Aspergilus niger, Candida
albicance, Fusarium oxysporum and Fusarium solani,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 7 2016

SYNTHESIS, ANTIMICROBIAL EVALUATION, AND DOCKING STUDIES
1715
Table 3. Antifungal activity of compounds 4a–4g and 5a–5g
a
b
Zone of inhibition (mm) and MIC (µg/mL)
Candida albicance Fusarium Oxysporum Fusarium Solani
Comp. no.
Aspergilus niger
4
a
09 (125)
21 (25)
5
17 (130)
19 (150)
23 (25)
8
09 (150)
19 (50)
17
4
b
18 (25)
4
c
11
4
d
11
6
6
13
No activity
9
4
e
No activity
9
No activity
3
4
f
14
5
4
5
g
a
21 (135)
No activity
20 (25)
23 (25)
15
22 (175)
8
28 (175)
No activity
21 (50)
19 (25)
14
21 (100)
9
5
b
19 (25)
22 (25)
6
18 (50)
25 (50)
12
5
c
5
d
5
e
22
25
32
20
5
f
9
19
15
12
5
g
10 (150)
22 (25)
No activity
13 (125)
22 (25)
No activity
08 (150)
23 (25)
No activity
18 (100)
20 (25)
No activity
Nystatin
Control (1% DMSO)
a
b
Zone of inhibition was measured for stock solution (100 µg/mL). Minimal inhibitory concentration (MIC) values of the selected
compounds are given in brackets. 1% DMSO was used as a control.
using Nystatin as reference drug and the results are
presented in Table 3. Among the fourteen compounds
screened for antifungal activity, compounds with more
electronegative substituent (4g and 5e) have shown
higher activity against Fusarium oxysporum and
Candida albicance than Nystatin. Compounds with
bromine 5c and chlorine 4b also exhibited maximum
activity against Fusarium Solani and Candida
albicance, respectively. Almost all the screened
compounds displayed good to moderate activity, that
may be explained as the whole molecular system is
responsible for the activity. Compounds 4d, 4e and 5a
have not shown any activity against Fusarium Solani,
Aspergilus niger and Fusarium Oxysporum. All the
results are summarized in Table 3. The MIC values
suggested that the compounds 4b and 4c were more
potent against fungal strains.
different inhibitors was observed. Active site of
adenosine-5'-(β,γ-imido) triphosphate protein (2ONJ)
[44] from S. Aureus and 1FY5 protein from Fusarium
Oxysporum [45] were used for the docking.
The binding energies of interaction follow the order
of the best fitness core. The highest fitness scored
compound was additionally subjected to compare of its
binding pattern and molecular interaction with the
standard drugs (Nystatin and Ciprofloxacin).
In view of the biological activity results obtained in
vitro, it was thought reasonable to perform molecular
docking studies to correlate both the results of in vitro
and in silico. The docking studies are used at different
stages of drug invention such as prediction a ligand-
receptor interaction and also to rank the titled com-
pounds based on the binding energies or fitness score.
In silico docking study. In the present study,
Version 2.0 of the GOLD(Genetic Optimization for
Ligand Docking) [41], SPDBV (Deep View/Swiss Pdb
Viewer 3.7) (SP5) [42] and the programs of Argus labs
In the present study, docking of the tested
compounds with the primary drug pathway for S.
aureus and Fusarium oxysporum was performed and
the corresponding fitness score was also determined as
shown in Table 4. The interacting energies followed
the order of the best fitness core. The highest fitness
scored compound was further subjected to evaluate its
[43] were used for docking. The interaction of the
ligands with the receptor in the modeled complexes
was investigated and the fitness function of proteins by
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 7 2016

1
716
SHANKAR et al.
Table 4. Gold fitness and chemscore of compounds 4a–4g
and 5a–5g
5a–5g within the active site of 2ONJ (Table 5).
Among several residues of the active site region TYR
3
91, GLU 121, ASN 385, SER 1057 play a key role of
Antibacterial
Antifungal
Comp. no.
formation of hydrogen bonds, which favours interact-
tion with 2ONJ protein. Molecular binding pattern of
4g revealed that it forms hydrogen bonds with TRY
391 and GLU 353 with hydrogen bond distances 2.94
and 2.28 Å (goldscore 69.75, chemscore 34.33).
Compound 5c showed hydrogen bonds with ASN 385
and SER 1057 with hydrogen bonding distance
between 2.99 and 2.88 Å (goldscore 88.25, chemscore
fitness chemscore fitness chemscore
4
a
72.38
73.92
72.64
70.57
70.81
71.02
69.75
80.84
68.83
88.25
84.00
77.49
–450.25
–396.82
–52
32.17
33.92
33.93
33.90
31.19
32.17
34.33
36.17
33.91
35.39
32.95
33.40
32.69
36.08
19.74
–
40.38
37.42
33.58
29.10
30.48
43.13
36.63
55.31
40.27
51.86
49.67
44.51
40.90
54.51
–
25.08
27.48
26.04
26.68
27.03
25.57
26.40
25.76
25.46
24.66
25.79
25.31
24.76
24.81
–
4
b
4
c
4
d
4
e
4
f
3
5.39). Similarly, 1FY5 protein from F. oxysporum
4
5
g
a
was chosen for the compounds with antifungal activity.
The molecular hydrogen binding pattern of 4b
revealed hydrogen bonds with ASN 101 with hydrogen
bond distances between 2.37 and 2.70 Å and HIS 91
and ASN 178 with bond distances of 2.37 and 2.73 Å
5
b
5
c
5
d
(
goldscore 33.42, chemscore 27.48). Compound 5c
5
e
showed hydrogen bonds distances 2.55 Å for SER164
and 2.57 Å for water molecule (HOH1170). Molecular
docking studies showed good correlation with the data
for in vitro biological activity. Among all, compounds
5
f
5
g
Ciprofloxacin
Nystatin
–
–25.70
0.59
4
g, 4b, and 5c showed the best affinities (gold fitness,
chemscore and arguslab binding energies) with used
proteins (2ONJ and 1FY5).
binding pattern and molecular interaction with the
standard drug (Nystatin and Ciprofloxacin)
Arguslab visualizer was used to visualize the
binding conformations of novel analogues 4a–4g and
Further supporting information, illustrating docking
experiments is available on demand from the authors.
Table 5. Argus labs energy values of compounds 4a–4g and 5a–5g (PDB ID: 2ONJ, 1FY5)
Argus labs energies (PDB ID: 1FY5) Argus labs energies (PDB ID: 2ONJ)
Argus B.E, kcal/mol GA dock energy, kcal/mol
Comp. no.
Argus B.E, kcal/mol
(elapsed time)
GA dock energy, kcal/mol
(elapsed time)
(elapsed time)
(elapsed time)
4
4
a
–8.0812 (7)
–9.4211 (6)
–8.2588 (6)
–8.2853 (6)
–8.4189 (6)
–8.6735 (6)
–9.7926 (6)
–8.7980 (7)
–5.1653 (4)
–8.8012 (5)
–7.8102 (6)
–5.6121 (3)
–6.6101 (4)
–5.6301 (3)
–5.6500 (9)
–9.3833 (12)
–4.8897 (7)
–6.4667 (8)
–8.2071 (10)
–5.5348 (8)
–8.6971 (10)
–8.6365 (13)
–8.30049 (13)
–8.0963 (12)
–7.5637 (13)
–9.7351 (13)
–7.9725 (13)
–4.7899 (12)
–16.1651 (33)
–16.3137 (21)
–15.1320 (26)
–15.2595 (27)
–15.6820 (26)
–15.4767 (22)
–16.0452 (25)
–15.4180 (12)
–16.0133 (10)
–15.6989 (11)
–15.8522 (10)
–13.0296 (8)
–9.3107 (9)
–10.9490 (16)
–10.6788 (17)
–13.7994 (15)
–13.3482 (16)
–11.7324 (15)
–11.5649 (16)
–14.7132 (16)
–11.2392 (18)
–12.6423 (19)
–13.1256 (20)
–12.9681 (20)
–12.7609 (19)
–10.3894 (19)
–11.7059 (19)
b
4
c
4
d
4
e
4
f
4g
5a
5b
5
c
5
d
5
e
5
f
5
g
–15.5551 (11)
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 7 2016

SYNTHESIS, ANTIMICROBIAL EVALUATION, AND DOCKING STUDIES
1717
EXPERIMENTAL
The filtrate was concentrated and the residue was
purified by chromatography using petroleum ether-
ethyl acetate mixture (10 : 1) as eluent to afford
compound 3 in 92% yield. White solid, mp 120–125°C.
Melting points were determined on a Casiae-Siamia
VMP-AM) melting point apparatus and are
(
–
1
–1
uncorrected. IR spectra (νmax, cm ) were recorded on a
IR spectrum, ν, cm : 2800 (C–H, aromatic), 1650
1
Perkin-Elmer FTIR 240-C spectrophotometer using
(C=C, aromatic), 1710 (C=O), 3550 (OH). H NMR
1
13
KBr pellets. H NMR and C NMR spectra were
recorded on a Bruker AV 300 MHz and AV 75 MHz
spectrum (DMSO-d ): 10.95 s (1H, Ar-OH), 9.85 s
6
(1H, CHO), 8.03 d (J = 7.93 Hz, 2H, Ar-H), 7.66–7.25
m (7H, Ar-H), 6.95 d (J = 8.39 Hz, 2H, Ar-H), 3.98 s
instruments, in CDCl3 or DMSO-d using TMS as an
6
1
3
internal standard. Chemical shifts are given in δ ppm
and coupling constants (J) are given in Hz. Electron
Spray Ionization (ESI) and high-resolution mass
spectra were recorded on a QSTARXL hybrid MS
system (Applied Bio Systems) under electro spray
ionization. Thin layer chromatography was performed
on pre-coated silica gel 60 F254 plates (Merck); spots
were visualized with UV light. All reagents and
chemicals of analytical grade were purchased from
Sigma-Aldrich chemical company and were used
without further purification.
(2H, CH2). C NMR spectrum (DMSO-d ): 198.3
6
(C=O), 160 (Ar-OH), 158.3, 138.9, 137.1, 135.8,
132.6, 131.8, 129.4, 128.5, 124.2, 112.6, 40.8 (CH ).
2
+
MS, m/z: 357.06 [M] .
Synthesis of (E)-3-{5-[(2-benzoylbenzofuran-5-
yl)methyl]-2-hydroxyphenyl}-1-phenylprop-2-en-1-
one (4a–4g) (general procedure). A solution of
compound 3 (0.1g, 0.33 mmol) and acetophenone
(
0.02 mol) in 25 mL of ethanol was treated with 10 mL
of 60% KOH solution at 5–10°C. The reaction mixture
was stirred at room temperature for 4 hours. It was
then diluted with water (50 mL) and extracted with
diethyl ether (3 × 20 mL). The aqueous solution was
acidified with diluted HCl. The solid obtained was
filtered off, washed thoroughly with water and purified
by crystallization from methanol [27].
In vitro antimicrobial assay. Antimicrobial activity
was evaluated using agar well diffusion method. The
activity was determined by measuring the diameter of
the inhibition zone (in mm). Samples of the tested
compounds (50 µL, 1 mg/mL concentation) were
loaded into the wells on the plates. All solutions were
prepared in DMSO and pure DMSO was loaded as
control. The plates were kept for incubation at 35°C
for 1–5 days and then were examined for the formation
of inhibition zone. Each inhibition zone was measured
three times to get an average value. The test was
performed three times for each bacterium culture
(
E)-3-{5-[(2-Benzoylbenzofuran-5-yl)methyl]-2-
hydroxyphenyl}-1-phenylprop-2-en-1-one (4a). Red
–
1
solid, yield 65 % mp 83–85°C. IR spectrum, ν, cm :
1
3
440, 3048, 1710, 1688, 1648, 1224. H NMR spec-
trum (DMSO-d ): 10.24 s (1H, OH), 8.10 d (1H, J =
6
1
5.81 Hz, β-H), 8.00 m (4H, Ar-H), 7.73–7.35 m
(
(
11H, Ar-H), 7.32 d (1H, J = 7.81 Hz, α-H), 7.06 d
1H, J = 8.01 Hz), 6.85 s (1H, Ar-H), 4.03 s (2H,
[38–40].
1
3
Minimal inhibitory concentration (MIC) measure-
CH2). C NMR spectrum (DMSO-d ): 192.4, 184.5,
6
ment. The microorganism’s susceptibility tests in
nutrient and potato dextrose broths were used for the
determination of MIC. Stock 1000 µg/mL solutions of
the tested compounds, ciprofloxacin and Nystatin were
prepared in DMSO followed by dilutions to 250–
155.1, 154.8, 152.4, 141.5, 138.3, 137.2, 133.4, 132.9,
132.4, 129.9, 129.4, 128.5, 124.7, 122.5, 117.3, 116.8,
112.4, 40.7. MS, m/z: 459 [M] .
+
(
E)-3-{5-[(2-Benzoylbenzofuran-5-yl)methyl]-2-
hydroxyphenyl}-1-(3,4-dichlorophenyl)prop-2-en-1-
2
5 µg/mL concentrations. Inoculated microorganism
one (4b). Brick red, yield 78%, mp 95–97°C. IR spec-
suspensions were incubated at 37°C for 1–5 days for
MIC determination [38–40].
–
1
1
trum, ν, cm : 3440, 3058, 1574, 1640, 1487, 1224. H
NMR spectrum (DMSO-d ): 10.24 s (1H, OH), 8.10 d
6
5
-[(2-Benzoylbenzofuran-5-yl)methyl]-2-hydroxy-
(1H, J = 16.01 Hz, β-H), 7.89 m (2H, Ar-H), 7.70–7.80
m (8H, Ar-H), 7.39 d (1H, J = 16.01, α-H), 7.29, s
(1H, Ar-H), 7.00–6.90 m (4H, Ar-H), 4.00 s (2H,
benzaldehyde (3). A mixture of 5,5'-methylenebis(2-
hydroxybenzaldehyde) (2) (0.02 mol), phenacylbro-
mide (0.02 mol) and K CO (0.017 mol) was stirred in
1
3
2
3
CH ). C NMR spectrum (DMSO-d ): 190.0, 182.01,
2
6
acetone (15 mL) at room temperature for 22 h [26]
After completion of the reaction, the deposit formed
was filtered off and washed with acetone (3 × 15 mL).
158.9, 154.7, 140.9, 138.2, 137.8, 133.1, 131.0, 128.9,
128.0, 124.2, 129.4, 118.4, 117.5, 116.5, 111.9, 42.0.
MS, m/z: 527 [M] .
+
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 7 2016

1
718
SHANKAR et al.
(
E)-1-(4-Aminophenyl)-3-{5-[(2-benzoylbenzo-
166.8, 166.1, 175.7, 154.3, 155.6, 141.2, 138.4, 133.5,
132.7, 131.0, 129.3, 127.5, 157.5, 124.5, 121.7, 119.6,
117.3, 116.8, 112.8, 104.8, 40.0. MS, m/z: 491 [M] .
furan-5-yl)methyl]-2-hydroxyphenyl}prop-2-en-1-
one (4c). Yellow solid, yield 78%; mp 52–53°C. IR
spectrum, ν, cm : 3400, 3055, 1589, 1649, 1474,
224. H NMR spectrum (DMSO-d ): 10.55 s (1H,
OH), 8.30 d (1H, J = 16.00 Hz, β-H), 7.88 s (2H, Ar-H),
.71–7.54 m (5H, Ar-H), 7.46 d (1H, J = 16.00 Hz,
α-H), 7.38 s (1H, Ar-H), 7.29–7.21 m (2H, Ar-H), 6.90–
.99 s (5H, Ar-H), 6.75 d (1H, J = 8.0 Hz, Ar-H), 6.5 s
2H, NH ), 4.0 s (2H, CH ). C NMR spectrum
DMSO-d ): 188.9, 180.2, 158.3, 155.9, 154.8, 154.0,
+
–
1
(
E)-3-{5-[(2-Benzoylbenzofuran-5-yl)methyl]-2-
hydroxyphenyl}-1-(4-bromophenyl)prop-2-en-1-one
4g). Brick red solid, yield 80%; mp 88–90°C. IR
1
1
6
(
7
–1
spectrum, ν, cm : 3410, 3058, 1580, 1659, 1474, 1224.
1
H NMR spectrum (DMSO-d ): 10.08 s (1H, OH),
6
6
(
(
1
1
8
7
.30 d (1H, J = 15.13 Hz, β-H), 8.01 s (1H, Ar-H),
.88–7.53 (9H, Ar-H), 7.71–7.54 m (5H, Ar-H), 7.42 d
1
3
2 2
6
(
1H, J = 15.13 Hz, α-H), 7.28 s (1H, Ar-H), 7.09–6.58
38.7, 137.5, 132.0, 131.7, 129.6, 128.7, 127.9, 124.8,
21.8, 120.0, 117.6, 116.8, 114.7, 112.0, 42.5. MS,
m/z: 474 [M] .
m (3H, Ar-H), 6.75 d (1H, J = 8.3 Hz, Ar-H), 3.92 s
13
(
2H, CH2). C NMR spectrum (DMSO-d ): 190.9,
6
+
1
82.2, 154.3, 153.9, 141.2, 138.7, 137.5, 132.0, 131.7,
(
E)-1-(3-Aminophenyl)-3-{5-[(2-benzoylbenzofuran-
128.7, 127.9, 124.8, 121.8, 120.0, 117.6, 112.0, 42.5.
MS, m/z: 537 [M] .
+
5
-yl)methyl]-2-hydroxyphenyl}prop-2-en-1-one (4d).
Yellow solid, yield 70 %; mp 95–97°C. IR spectrum
Synthesis of {5-[4-hydroxy-3-(4-phenyl-2,3-di-
hydro-1H-benzo[b][1,4]diazepin-2-yl)benzyl]benzo-
furan-2-yl}(phenyl)methanones (5a–5g) (general
procedure). A mixture of α,β-unsaturated ketone
–
1
(
KBr), ν, cm : 3422, 3051, 1584, 1649, 1484, 1214.
1
H NMR spectrum (DMSO-d ): 10.50 s (1H, OH),
6
8
7
.10 d (1H, J = 16.25 Hz, β-H), 7.88 s (2H, Ar-H),
.60–7.70 m (7H, Ar-H), 7.40 d (1H, J = 16.25 Hz, α-
(
chalcone) (4a) (0.15 g, 0.33 mmol) and o-phenylene-
diamine (0.047 g, 0.49 mmol) in oxalic acid–DMF
20 mol %) was heated at 80°C for 3 h [28]. After
H), 7.28 s (1H, Ar-H), 7.69–7.90 m (3H, Ar-H), 6.55 s
13
(
2H, Ar-H), 6.30 s (2H, NH ), 3.98 s (2H, CH ).
C
2
2
(
NMR spectrum (DMSO-d ): 187.9, 182.2, 178.3,
6
completion of the reaction (monitored by TLC), the
reaction mixture was cooled to room temperature and
extracted with ethyl acetate (3 × 10 mL). The com-
bined organic layers were dried over anhydrous
1
1
1
65.9, 154.8, 134.0, 198.7, 187.5, 132.0, 131.7, 129.6,
98.7, 128.9, 122.8, 121.8, 120.0, 115.6, 146.8, 114.7,
32.0, 40.9. MS, m/z: 474.0 [M] .
+
(
E)-3-{5-[(2-Benzoylbenzofuran-5-yl)methyl]-2-
Na SO . The solvent was removed and the solid re-
2 4
hydroxyphenyl}-1-(3-hydroxyphenyl)prop-2-en-1-
sidue was purified on silica gel column (2.5 × 45 cm),
prepacked in chloroform. Elution with petroleum
ether : ethyl acetate (18 : 2) mixture gave a homo-
geneous residue which was concentrated in vacuum to
give compound 5a. Brick red, yield 87%; mp 115–
one (4e). White solid, yield 62%; mp 95–100°C. IR
–
1
spectrum, ν, cm : 3440, 3042, 1579, 1645, 1486,
1
1
224. H NMR spectrum (DMSO-d ): 10.400 s (2H,
6
OH), 8.20 d (1H, J = 16.01 Hz, β-H), 8.00 d (2H, J =
.4 Hz, Ar-H), 7.78–7.22 m (10H, Ar-H), 7.40 d (1H,
J = 16.01 Hz, α-H), 6.90–6.70 m (3H, Ar-H), 6.75 d
–
1
8
118°C. IR spectrum, ν, cm : 3498 (OH), 3324 (NH),
3075 (CHarom), 1795 (C=O), 1609 (C=N), 1591 (C=C).
1
3
1
(
1H, J = 8.42 Hz, Ar-H), 4.03 s (2H, CH ). C NMR
H NMR spectrum (DMSO-d ): 10.40 s (1H, OH),
2
6
spectrum (DMSO-d ): 195.5, 182.7, 162.9, 155.7,
8.01 m (2H, Ar-H), 7.98 d (J = 8.1 Hz, 2H, Ar-H),
7.80 d (J = 7.7 Hz, 2H, Ar-H), 7.70–7.43 m (8H, Ar-H),
7.44–7.14 m (2H, Ar-H), 7.04–6.68 m (5H, Ar-H),
6
1
1
41.2, 137.9, 131.0, 128.5, 127.5, 124.5, 123.8, 121.9,
19.6, 117.3, 116.8, 112.8, 40.0. MS, m/z: 475 [M] .
+
4
.01 s (1H, NH), 3.95 s (1H, CH ), 3.75 t (1H,
2
(
E)-3-{5-[(2-Benzoylbenzofuran-5-yl)methyl]-2-
hydroxyphenyl}-1-(2,4-dihydroxyphenyl)prop-2-en-
-one (4f). Off white solid, yield 65%; mp 91–92°C.
benzylic-CH), 2.02 d (J = 12.8 Hz, 1H, allylic-CH),
1
spectrum (DMSO-d ): 183.0, 164.2, 159.3, 155.2,
150.5, 145.2, 144.5, 140.8, 138.5, 137.6, 133.9, 132.7,
1
1
5
1
3
.99 d (J =12.8 Hz, 1H, allylic-CH). C NMR
1
–
1
6
IR spectrum, ν, cm : 3440, 3042, 1569, 1645, 1489,
221. H NMR spectrum (DMSO-d ): 10.55 s (3H,
OH), 8.33 d (1H, J =16.10 Hz, β-H), 7.86–7.98 d (3H,
J = 7.5 Hz, Ar-H), 7.78–7.54 m (5H, Ar-H), 7.48 d
1H, J = 16.10 Hz, α-H), 7.29 s (1H, Ar-H), 6.90–6.70
1
1
6
31.0, 129.7, 128.0, 128.2, 128.8, 126.7, 123.9, 121.8,
19.9, 116.9, 116.2, 112.0, 56.0, 40.0, 38.0. MS, m/z:
+
49.4 [M] .
(
m (3H, Ar-H), 6.758 d (1H, J = 8.42 Hz, Ar-H), 6.48 d
{5-[4-Hydroxy-3-(8-methyl-4-phenyl-2,3-dihydro-
(
(
1H, J = 7.58 Hz, Ar-H), 6.21 s (1H, Ar-H), 4.03 s
1H-benzo[b][1,4]diazepin-2-yl)benzyl]benzofuran-
2-yl}(phenyl)methanone (5b). Yellow crystals, yield
13
2H, CH ). C NMR spectrum (DMSO-d ): 193.5, 182.7,
2
6
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 7 2016

SYNTHESIS, ANTIMICROBIAL EVALUATION, AND DOCKING STUDIES
1719
–
1
8
(
1
(
5%; mp 116–120°C. IR spectrum, ν, cm : 3498
{5-[4-Hydroxy-3-(8-nitro-4-phenyl-2,3-dihydro-
1H-benzo[b][1,4]diazepin-2-yl)benzyl]benzofuran-
2-yl}(phenyl)methanone (5e). Yellow solid, yield
OH), 3295 (NH), 3075 (CHarom), 1786 (C=O), 1619,
590 (C=C). H NMR spectrum (DMSO-d ): 10.30 s
6
1H, OH), 7.91 m (4H, Ar-H), 7.98 d (J = 8.5 Hz, 2H,
Ar-H), 7.80 d (J = 8.0 Hz, 2H, Ar-H), 7.73–7.53 m
8H, Ar-H), 7.29 s (1H, Ar-H), 7.04–6.68 m (3H,
1
–
1
72%; mp 115–118°C. IR spectrum, ν, cm : 3410
(OH), 3467 (NH), 3138 (CHarom), 1799 (C=O), 1659
1
(
(C=C), 1623.6 (C=N). H NMR spectrum (DMSO-d ):
6
Ar-H), 4.12 s (1H, NH), 4.05 s (1H, CH ), 3.79 t (1H,
10.58 s (1H, OH), 8.05 d (J = 8.5 Hz, 2H, Ar-H), 7.80
d (J = 8.0 Hz, 2H, Ar-H), 7.80–7.50 m (9H, Ar-H),
7.45 s (1H, Ar-H), 6.85 d (J = 7.55 Hz, 2H, Ar-H),
6.44–6.38 d (J = 8.1 Hz, 1H, Ar-H), 6.20–6.18 s (1H,
2
benzylic-CH), 2.5 s (3H, CH ), 2.05 d (J =12.5 Hz,
3
1
H, allylic-CH), 2.00 d (J = 12.5 Hz, 1H, allylic-CH).
1
3
C NMR spectrum (DMSO-d ): 183.5 (CO), 166.8
6
(
C=N), 160.5, 156.8, 150.0 (C–OH), 145.1, 144.5,
Ar-H), 4.08 s (1H, NH), 3.89 s (2H,CH ), 3.80 t (1H,
2
1
1
1
39.3, 138.8, 137.0, 136.9, 136.6, 133.9, 132.9, 132.0,
30.7, 129.9, 129.3, 128.2, 127.9, 124.6, 120.8, 116.9,
16.2, 112.0, 55.0. MS, m/z:563.3 [M] .
benzylic-CH), 2.10 d (J 12.5 Hz, 1H, allylic-CH), 2.01
1
3
d (J 12.5 Hz, 1H, allylic-CH). C NMR spectrum
(DMSO-d ): 183.2 (CO), 168.7 (C=N), 161.5 (benzo-
furan C–O), 157.8 (furan C–O), 152.0 (C–OH), 149.1
C–NO ), 143.4, 139.9, 137.8, 137.0, 13697, 135.6,
+
6
{
5-[3-(8-Bromo-4-phenyl-2,3-dihydro-1H-benzo-
(
2
[
b][1,4]diazepin-2-yl)-4-hydroxybenzyl]benzofuran-
1
33.9, 132.1, 131.9, 130.8, 129.6, 129.3, 128.2, 126.1,
2
8
-yl}(phenyl)methanone (5c). Light yellow, yield
–
1
123.8, 120.8, 115.9, 116.1, 112.0, 57.9, 41.1, 40.0.
7%; mp 115–118°C. IR spectrum, ν, cm : 3482
+
MS, m/z: 594.2 [M] .
(
OH), 3477 (NH), 3138, 1799 (C=O), 1651 (C=C),
1
1
623.6 (C=N). H NMR spectrum (DMSO-d ): 10.55 s
{5-[3-(7,8-Dimethyl-4-phenyl-2,3-dihydro-1H-
benzo[b][1,4]diazepin-2-yl)-4-hydroxybenzyl]benzo-
furan-2-yl}(phenyl)methanone (5f). Brick red, yield
6
(
8
(
1H, OH), 8.01 d (J = 8.5 Hz, 2H, Ar-H), 7.87 d (J =
.1 Hz, 2H, Ar-H), 7.75–7.54 m (8H, Ar-H), 7.59 s
1H, Ar-H), 7.87 d (J = 8.1 Hz, 1H, Ar-H), 7.04–6.98
d (J = 8.1 Hz, 3H, Ar-H), 6.88–6.64 m (3H, Ar-H),
.04 s (1H, NH), 4.0 s (1H, CH ), 3.79 t (1H, benzylic-
–
1
75%; mp 105–106°C. IR spectrum, ν, cm : 3449
(OH), 3298 (NH), 3071, 1756 (C=O), 1611, 1590
1
4
(C=C). H NMR spectrum (DMSO-d ): 10.30 s (1H,
2
6
CH), 2.07 d (J = 11.8 Hz, 1H, allylic-CH), 1.98 d (J =
OH), 7.93 d (J = 8.5 Hz, 2H, Ar-H), 7.98 d (J =
7.5 Hz, 2H, Ar-H), 7.73–7.58 m (8H, Ar-H), 7.20 s
(1H, Ar-H), 7.04–6.68 m (5H, Ar-H), 6.40 s (1H, Ar-
13
1
1.8 Hz, 1H, allylic-CH) C NMR spectrum (DMSO-
d6): 183.7 (CO), 166.7 (C=N), 161.5, 157.8, 150.0
C–OH), 147.1, 143.4, 139.9, 137.8, 137.0, 13697,
(
H), 4.12 s (1H, NH), 4.05 s (1H, CH ), 3.79 t (1H,
2
1
1
4
35.6, 133.9, 132.1, 131.9, 130.8, 129.6, 129.3, 128.2,
26.1, 123.8, 120.8, 115.9, 116.1, 112.0, 57.9, 41.1,
0.0. MS, m/z: 628.5 [M] .
benzylic-CH), 2.6 s (6H, 2CH ), 2.11 d (J = 11.5 Hz,
3
1H, allylic-CH), 2.03 d (J = 11.5 Hz, 1H, allylic-CH).
+
13
C NMR spectrum (DMSO-d ): 183.5 (CO), 167.8
6
(
1
1
C=N), 161.5, 156.8, 150.0 (C–OH), 145.1, 144.5,
39.3, 138.8, 137.0, 136.9, 136.6, 133.9, 132.9, 132.0,
30.7, 129.9, 129.3, 128.2, 127.9, 124.6, 120.8, 116.9,
{
5-[3-(7,8-Dichloro-4-phenyl-2,3-dihydro-1H-
benzo[b][1,4]diazepin-2-yl)-4-hydroxybenzyl]benzo-
furan-2-yl}(phenyl)methanone (5d). Red solid, yield
2%; mp 125–128°C. IR spectrum, ν, cm : 3477
OH), 3497 (NH), 3130, 1798 (C=O), 1651 (C=C),
629.6 (C=N). H NMR spectrum (DMSO-d ): 10.56 s
6
–
1
116.2, 112.0, 55.0, 40.6, 35.7, 22.3. MS, m/z: 577.3
[
6
(
1
+
M] .
1
{5-[3-(8-Fluoro-4-phenyl-2,3-dihydro-1H-benzo-
(
8
(
7
1H, OH), 8.03 d (J = 8.5 Hz, 2H, Ar-H), 7.88 d (J =
.1 Hz, 2H, Ar-H), 7.79–7.44 m (8H, Ar-H), 7.39 s
1H, Ar-H), 7.20 d (1H, Ar-H), 7.04–6.98 d (J =
.51 Hz, 2H, Ar-H), 6.88–6.64 m (2H, Ar-H), 4.04 s
1H, NH), 4.0 s (1H, CH ), 3.79 t (1H, benzylic-CH),
[b][1,4]diazepin-2-yl)-4-hydroxybenzyl]benzofuran-
2-yl}(phenyl)methanone (5g). Yellow solid, yield
89%; mp 118-121°C. IR spectrum, ν, cm : 3480
–
1
(OH), 3425 (NH), 3133, 1799 (C=O), 1651 (C=C),
1
(
1613 (C=N). H NMR spectrum (DMSO-d ): 10.55 s
2
6
2
1
.01 d (J = 12.8 Hz, 1H, allylic-CH), 1.97 d (J =
2.8 Hz, 1H, allylic-CH). C NMR spectrum (DMSO-
(1H, OH), 8.08 d (J = 8.7 Hz, 2H, Ar-H), 7.89 d (J =
7.9 Hz, 2H, Ar-H), 7.79–7.64 m (8H, Ar-H), 7.49 s
(1H, Ar-H), 7.87 d (J = 8.5 Hz, 3H, Ar-H), 7.04–6.98
d (J = 8.1 Hz, 3H, Ar-H), 6.88–6.84 m (2H, Ar-H),
6.54 s (2H, Ar-H), 4.05 s (1H, NH), 3.98 s (1H, CH2),
3.90 t (1H, benzylic-CH), 2.04 d (J = 13.01 Hz, 1H,
13
d6): 183.0 (CO), 166.9 (C=N), 161.5, 157.8, 151.0
C–OH), 147.1, 144.4, 139.9, 138.8, 137.5, 136.7,
(
1
1
34.6, 133.9, 132.9, 131.0, 130.8, 129.9, 129.3, 128.2,
26.9, 124.8, 120.8, 115.9, 112.0, 57.5, 40.1, 40.2.
+
13
MS, m/z: 617.5 [M] .
allylic-CH), 1.87 d (J = 13.01 Hz, 1H, allylic-CH). C
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 7 2016

1
720
SHANKAR et al.
NMR spectrum (DMSO-d ): 182.7 (CO), 166.5 (C=N),
p. 1125.
6
1
60 (benzofuran C–O), 159.5 (furan C–O), 150.9
6. De Meyer, N., Haemers, A., Mishra, L., Pandey, H.K.,
Peters, L.A., Vanden Berghe, D.A., and Vlietinck, A.J.,
J. Med. Chem., 1991, vol. 34, p. 736. DOI: 10.1021/
jm00106a700.
7. Ducki, S., Forrest, R., Hadfield. J., Kendall, A.,
Lawerence, N.J., McGrown, A.T., and Rennison, D.,
Bioorg. Med. Chem. Lett., 1998 vol. 8, p. 1051.
DOI: DOI: 10.1016/S0960-894X (98)00162-0.
(
C–OH), 149.8, 144.1, 138.3, 137.8, 137.0, 134.8,
1
1
32.5, 130.5, 129.7, 128.9, 127.8, 124.7, 124.1, 120.4,
18.5, 116.1, 105.9, 103.5, 57.1 (C-NH), 42.5, 35.9.
+
MS, m/z: 567.0 [M] .
Supportin vaterials are available from authors.
CONCLUSIONS
8. Mei-Lin, Go., Liu Mei., Wilairat, P., Rosenthal, P.J.,
Saliba, K.J., and Kirk, K., Antimicrob Agents
Chemother., 2004, vol. 48, p. 3241. DOI: 10.1128/
AAC.48.9.3241-3245.2004.
We have synthesized novel chalcones, 1,4 benzo-
diazepines molecules, representative examples were
screened in vitro antimicrobial activity. The biological
evolution of these molecules 4a–4g and 5a–5g showed
good antimicrobial activities. Among all compounds
9. Azam, A., Hayat, F., Mosely, E., Attar, S., and Vanzyl, R.,
Eur. J. Med. Chem., 2011, vol. 46, p. 1897. DOI:
1
0.1016/j.ejmech.2011.02.004.
1
1
1
1
0. Satyanarayana, M., Tiwari, P., Tripathi, B.K.,
4
5
g and 5g showed potent antibacterial activity, 4b and
g showed good antifungal activity. Most of the
Srivastava, A.K., and Pratap, R., Bioorg. Med. Chem.,
2
004, vol. 12, p. 883. DOI: 10.1016/j.bmc.2003.12.026.
biological experimental values are correlated with
docking results. These molecular binding interactions
of an in silico data demonstrated that above has more
specificity towards the (2ONJ) & (1FY5) binding site
and could be a potent in vitro antimicrobial compound.
However, in this research article, regarding the
obtained results, molecular docking analysis suggested
that the compounds 4b, 4g, and 5c could serve as an
appropriate starting point for designing new chemical
entities as potent S. aureus and Fusarium oxysporum
inhibitors.
1. Padhyee, S., Ahmad, A., Oswal, N., and Sarkar, F.H.,
J. Hematol. Oncol., 2009, vol. 2, p. 38. DOI:
1
0.1186/1756-8722-2-38.
2. Iwalewa, E.O., Oyedapo, O.A., Adewunmi, C.O., and
Makunja, V.O., J. Biol. Sci., 2008, vol. 8, p. 131.
DOI: 10.3923/jbs.2008.131.136.
3. Nam, N.H., Kim, Y., You, Y.J., Hong, D.H.,
Kim, H.M., and Ahn, B.Z., Eur. J. Med. Chem., 2003,
vol. 38, p. 179. DOI: 10.1016/S0223-5234(02)01443-5.
14. Dimmock, J.R., Ellas, D.W., Beazely, M.A., and
Kandepu, N.M., Curr. Med. Chem., 1999, vol. 6,
p. 1125.
ACKNOWLEDGMENTS
15. Khan, M.W., Alam, M.J., Rashid, M.A., and
Chowdhury, R. A., Bioorganic & Medicinal Chemistry.,
2005, vol. 13, p. 4796. DOI: 10.1016/j.bmc.2005.05.009.
16. Buu-Hoi, N.P., Bisagni, E., Royer, R., and Routier, C.,
J. Chem. Soc., 1957, p. 625. DOI: 10.1039/JR9570000625.
17. Buu-Hoi, N., Saint-Ruf, G., Loc, T.B., and Xuong, N.D.,
J. Chem. Soc., 1957, p. 2593. DOI: 10.1039/JR9570002593.
B. Shankar thanks UGC-BSR (RFSMS), New
Delhi, India, for financial supports in the form of
senior research fellowship (SRF) and also thanks IICT
Indian Institute of Chemical Technology), Hyderabad,
India, for providing analytical support.
(
1
1
2
8. Benkli, K., Gundogdu-Karaburun, N., Karaburun, A.C.,
Ucucu, U., Demirayak, S., and Kiraz, N., Eur. J. Med.
Chem., 2006, vol. 41, p. 651. DOI: 10.1016/
j.ejmech.2005.12.013.
9. Baraldi, P.G., Romagnoli, R., Beria, I., Geroni, P.C.,
Mongelli, N., Bianchi, N., Mischiati, C., and Gambari, R.,
J. Med. Chem., 2000, vol. 43, p. 2675. DOI: 10.1021/
jm9911229.
0. Chandrashekar. A., Eswarappa, B., Yadav, D.B.,
Venkatesh, K.B., Raghu, N., and Shivakumar, M.C.,
Med. Chem. Res., 2013, vol. 22, p. 78. DOI: 10.1007/
s00044012-0017-y.
REFERENCES
1
. Xue-Quan Wang, Lan-Xiang Liu, Yan Li, Cheng-Jun
Sun, Wen Chen, Liang Li, Hong-Bin Zhang, Xiao-Dong,
and Yang, Eur. J. Med. Chem., 2013, vol. 62, pp 111.
DOI: 10.1016/j.ejmech.2012.12.040.
. Yuhong, J.U. and Varma, R.S.J., J. Org. Chem., 2006,
vol. 71, p. 135. DOI: 10.1021/jo051878h.
. Sarma, B.K., Mishra, P.K., Singhai, P.K., and
Singh, U.P., Mycobiology., 2007, vol. 35, p. 72.
DOI: 10.4489/MYCO.2007.35.2.072.
2
3
4
. Parikh, K.S. and Joshi, D.S., Med. Chem. Res., 2013,
vol. 22, p. 3688. DOI: 10.1007/s004412-0369-3.
21. Middlemiss, D., Drew, G.M., Ross, B.C., Robertson, M.J.,
Scopes, D.C., Dowle, M. D., Hamblett, J., Cardwell, K.,
Clark, K. L., Coote, S., Eldred, C.D., Hamblett, J.,
Hilditch, A., Hirst, G.C., Jack, T., Montona, J., Pan-
5. Dimmock, J.R., Ellas, D.W., Beazely, M.A., and
Kandepu, N.M., Curr. Med. Chem., 1999, vol. 6(12),
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 7 2016

SYNTHESIS, ANTIMICROBIAL EVALUATION, AND DOCKING STUDIES
1721
chal, T.A., Paton, S.M., Shah, P., Stuart, G., and
Travers, A., Bio. Med. Chem. Lett., 1991, vol. 1, p. 711.
DOI: 10.1016/S0960-894X(01)81053-2.
34. Jadhav, S.B., Shasthri, R.A., Bagul, K.R., and Gai-
kwad, K.V., Indian. J. Het. Chem., 2009, vol. 18,
p. 319. DOI: 10.9790/5736-09227175.
2
2
2. Leung, A.Y. and Foster, S.W., Encyclopedia of
Common Natural Ingredients Used in Food, Drugs, and
Cosmetics, New York: Wiley, 1996, vol. 35, p. 648.
3. Elvers, B., Hawkins, S., and Schulz, G., Optical
Brighteners, Weinheim: VCH, 1999, vol. A18, p. 153,
35. Marvel, C.S. and Tarkoy, N.J., Am. Chem. Soc., 1957,
vol. 79, p. 6000. DOI: 10.1021/ja01579a041.
3
3
6. Thool, A.W. and Ghiya, B.J.J., Indian Chem. Soc.,
1988, vol. 65, p. 522.
7. Aniket, P.S., Jaiprakashn, S., Nanasahe, B.B.D.,
Ajinkya, P.S., Paravani, S.W., and Devanand, B.S.,
J. Chil. Chem. Soc., 2013, vol. 58, p. N4. DOI: 10.4067/
S0717-97072013000400064.
5
ed.
2
2
4. Antoine, M., Barreu, M., Desconclois, J.F., Girard, P.,
and Picaut, G., Chem. Abstr., 1991, vol. 114, p. 14339.
5. Kusanur, R., Ghate, M., and Kulkurani, M., J. Chem.
Sci., 2004, vol. 116, p. 265. DOI: 10.1007/BF02708277.
3
8. Bhavanarushi, S., Kanakaiah, V., Gandu, B., Ganga-
gnirao, A., and Vatsala, R., Med. Chem. Res., 2014,
vol. 23(1), p. 158. DOI: 10.1007/s00044-013-0623-3.
2
2
6. Basawaraj, R., Naubade, K., and Sangapure, S.S.,
Indian. J. Heterocycl. Chem., 2008, vol. 17, p. 217.
39. Patel, M.A., Bhila, V.G., Patel, N.H., Patel, A.K., and
Brahmbhatt, D.I., Med. Chem. Res., 2012, vol. 21,
p. 4381. DOI: 10.1007/s00044-012-9978-0.
7. Grossi, G., Braccio, M.D., and Calcina, F., Eur. J. Med.
Chem., 2002, vol. 37, p. 933. DOI: 10.1016/S0223-5234
(
02)01400-9.
40. Keche, A.P., Hatnapure, G.D., Tale, R.T., Rodge, A.H.,
Birajdar, S.S., and Kamble, V.M., Med. Chem. Res.,
2
2
3
8. Kusanur, A.R., Ghate, M., and Kulkarni, V.M.,
J. Chem. Sci., 2004, vol. 11, p. 265. DOI: 10.1007/
BF02708277.
2013, vol. 22, p. 1480. DOI: 10.1007/s00044-012-0144-5.
41. Jones, G. and Willett, P., Glen, R.C., J. Mol. Biol.,
1
8
995, vol. 43, p. 245. DOI: 10.1016/S0022-2836(95)
0037-9.
9. Jauhari, P.K., Bhavani, A., Varalwar, S., Singhal, K.,
Raj, P., Med. Chem. Res., 2008, vol. 17, p. 412.
DOI: 10.1007/s00044-007-9076-x.
0. Mahajan, A., Kumar, V., Mansour, N.R.N., Bickle, Q.,
and Chibale, K., Bioorg. Med. Chem. Lett., 2008,
vol. 18, p. 2333. DOI: 10.1016/j.bmcl.2008.02.077.
4
2. Verdonk, M.L., Cole, J.C., Hartshorn, M.J., Murray, C.W.,
and Taylor, R.D., Struct. Funct. Bioinform., 2003,
vol. 52, p. 609. DOI: 10.1002/prot.10465.
43. Trott, O. and Olson, A.J., J. Comp. Chem., 2010,
vol. 31, p. 455. DOI: 10.1002/jcc.21334.
3
3
1. Drabu, S. and Kumar, N., Asian. J. Chem., 2007,
vol. 19, p. 5743.
44. Dawson, R.J.P. and Locher, K.P., FEBS Lett., 2007,
vol. 581, p. 935. DOI: 10.1016/j.febslet.2007.01.073.
2. Fred, E.D., Byung, H.L., Sandra, S.J., and Eileen, M.C.,
J. Med. Chem., 2003, vol. 46, p. 2057. DOI: 10.1021/
jm020482k.
45. Rypniewski, W.R., Ostergaard, P.R., Norregaard-
Madsen, M., Dauter, M., and Wilson, K.S., Acta
Crystallogr., Sect. D, 2001, vol. 57, p. 8. DOI: 10.1107/
S0907444900014116.
3
3. Gandhi, M. and Olyaei, A., J. Het. Chem., 2007, vol. 44,
p. 323. DOI: 10.1002/jhet.5570440207.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 7 2016