An Efficient Microwave-Assisted Synthesis of Novel 2-{4-[(3-Aryl-1,8-naphthyridin-2-yl)amino]phenyl}-1H-benzo[de]isoquinoline-1,3(2H)-diones and Their Antimicrobial Activity

Article abstract of DOI:10.1134/S1070363218040242

The Buchwald–Hartwig amination reaction between 2-chloro-3-aryl-1,8-naphthyridines and 2-(4-aminophenyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione in the presence of the catalytic system Pd(PPh₃)₄ and the base KO-t-Bu in toluene was studied. The reaction was initiated by microwave irradiation. Highly efficient synthesis has been developed for 2-{4-[(3-aryl-1,8-naphthyridin-2-yl)amino]phenyl}-1H-benzo[de]isoquinoline-1,3(2H)-diones. Structures of the synthesized compounds were evaluated by IR, ¹H and ¹³C NMR spectroscopy. All products were tested for antimicrobial activity against Escheria coli, Bacillus subtilis, Klebsiella pneumoniae, and Staphylococcus aureus.

Full text of DOI:10.1134/S1070363218040242

ISSN 1070-3632, Russian Journal of General Chemistry, 2018, Vol. 88, No. 4, pp. 780–788. © Pleiades Publishing, Ltd., 2018.
An Efficient Microwave-Assisted Synthesis
of Novel 2-{4-[(3-Aryl-1,8-naphthyridin-2-yl)amino]phenyl}-
1H-benzo[de]isoquinoline-1,3(2H)-diones
and Their Antimicrobial Activity1
B. Sakrama*, D. Ravia, K. Ashoka S. Rambabua, B. Sonyanaika, and A. Kurumannaa
a Department of Chemistry, Osmania University, Hyderabad, 500007 India
*e-mail: bschemou@gmail.com
Received November 15, 2017
Abstract—The Buchwald–Hartwig amination reaction between 2-chloro-3-aryl-1,8-naphthyridines and 2-(4-
aminophenyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione in the presence of the catalytic system Pd(PPh3)4 and
the base KO-t-Bu in toluene was studied. The reaction was initiated by microwave irradiation. Highly efficient
synthesis has been developed for 2-{4-[(3-aryl-1,8-naphthyridin-2-yl)amino]phenyl}-1H-benzo[de]isoquino-
1
line-1,3(2H)-diones. Structures of the synthesized compounds were evaluated by IR, H and 13C NMR
spectroscopy. All products were tested for antimicrobial activity against Escheria coli, Bacillus subtilis,
Klebsiella pneumoniae, and Staphylococcus aureus.
Keywords: Antimicrobial activity, C–N bond formation, microwave irradiation, molecular docking,
1,8-naphthyridine, Pd(PPh3)4 catalyst
DOI: 10.1134/S1070363218040242
INTRODUCTION
Microwave-assisted organic synthesis is now a well-
established procedure in organic synthesis [20–22]. In
such procedures solvents with higher dielectric
constants are superheated and the reactions proceed
rapidly. In view of the above information and as a
development of our earlier studies of microwave-
assisted processes with 1,8-naphthyridine derivatives
[23], we report herein a new efficient procedure for the
synthesis of 2-{4-[(3-aryl-1,8-naphthyridin-2-yl)amino]-
phenyl}-1H-benzo[de]isoquinoline-1,3(2H)-diones
(9a–9h) (Scheme 1).
1,8-Naphthyridine derivatives isolated from natural
sources demonstrated various biological activities
[1–3]. Nalidixic acid, for example, possesses robust
antibacterial activity and is used mostly against gram
negative pathogens of urinary tract infections [4].
Vosaroxin is a naphthyridine analog of the anticancer
quinolones [5]. Gemifloxacin is an antimicrobial and
antibacterial agent [6]. Also, 1,8-naphthyridines and
their dimer derivatives have been studied in host-guest
and self-assembling systems [7] (Fig. 1).
RESULTS AND DISCUSSION
The rising interest in synthesis of 1,8-napht-
hyridines [8] was initiated by their biological activities
including antitumor [9], anti-inflammatory [10, 11],
Condensation of 2-aminonicotinaldehyde (1) with
2-phenylacetonitrile (2) in the presence of piperidine
without a solvent at room temperature resulted in
formation of 2-amino-1,8-naphthyridines (3), which
was converted into 1,8-naphthyridine-2(1H)-ones (4)
by the reaction with NaNO2. Refluxing of compounds
4 with POCl3 afforded 2-chloro-1,8-naphthyridines (5)
[24]. Condensation of benzene-1,4-diamine (6) with
benzo[de]isochromene-1,3-dione (7) in the presence of
methanol upon refluxing afforded 2-(4-aminophenyl)-
1H-benzo[de]isoquinoline-1,3(2H)-dione (8) [25].
anticonvulsant [12], and antihypertensive
[13, 14].
Some 1,8-naphthyridine mixtures have been patented
as efficient agrochemicals [15, 16]. Palladium
catalyzed coupling of aryl halides with amine nucleo-
philes in the presence of stoichiometric amounts of a
base was reported in 1955 [17]. This was developed
further later on [18, 19].
1 The text was submitted by the authors in English.
780

AN EFFICIENT MICROWAVE-ASSISTED SYNTHESIS
781
O
O
O
O
F
OH
OH
N
N
N
N
HN
F
H2N
S
N
O
O
F
Vosaroxin
Trovafloxacin
O
O
O
F
OH
OH
H3C O
N
N
N
H3C
N
N
Et
H2N
Nalidixic Acid
Gemifloxacin
Fig. 1. Chemical structure of the some active 1,8-naphthyridines.
R
R
O
R
H
1
2
+
+
N
NH2
N
N
NH2
N
N
H
O
CN
2
1
3a−3h
4a−4h
R
3
NH2
O
O
O
O
N
O
4
+
NH2
N
N
Cl
NH2
6
7
8
5a−5h
5
R
O
N
O
N
H
N
N
9a−9h
Scheme 1. Synthesis pathway of the compounds 3a–3h to 9a–9h.
R = H (3a–5a, 9a); o-CF3 (3b–5b, 9b); p-OCH3 (3c–5c, 9c); o-OCH3 (3d–5d, 9d); p-Cl (3e–5e, 9e); p-F (3f–5f, 9f); p-Br
(3g–5g, 9g); p-NO2 (3h–5h, 9h). Reagents and conditions: (1) piperidine, (2) NaNO2, room temperature to reflux; (3) POCl3;
(4) MeOH, reflux; (5) Pd(PPh3)4, KO-tert-Bu, toluene, microwave.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 4 2018

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SAKRAM et al.
Table 1. Synthesized C–N bond formations of C3 substituted 1,8-naphthyridine ring (9a–9h)
Comp. no. 2-Chloro-3-aryl-1,8-naphthyridines Product no.
Product 9a
Time, min Yieldb, %
5a
9a
4.5
82
O
N
O
N
N
N
N
N
Cl
H
F3C
F3C
5b
9b
4.0
80
O
N
N
Cl
N
N
N
N
O
H
O
O
5c
9c
4.5
76
CH3
O
CH3
N
N
Cl
N
N
N
H
N
O
O
O
5d
5e
5f
9d
9e
9f
4.0
4.0
3.5
69
81
80
H3C
H3C
N
O
N
O
N
N
N
Cl
Cl
N
N
N
N
H
Cl
F
Cl
F
O
N
O
N
N
N
N
H
O
N
O
N
N
Cl
N
H
Br
Br
5g
5h
9g
9h
3.5
4.0
69
78
O
N
O
N
N
N
N
Cl
Cl
N
N
N
N
N
H
NO2
NO2
O
N
H
N
O
a IR, 1H, 13C NMR, and MS spectra were proven with the assigned structures of all new compounds. b Isolated yield after work up.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 4 2018

AN EFFICIENT MICROWAVE-ASSISTED SYNTHESIS
783
Scheme 2. Proposed mechanism of preparation of 2-{4-[(3-aryl-1,8-naphthyridin-2-yl)amino]phenyl}-1H-benzo[de]isoquino-
line-1,3(2H)-diones (9a–9h).
R
R
O
N
N
N
N
O
H
Pd0 (PPh3)4
Cl
R
N
N
Oxidative
addition
Reductive
elimination
R
(Ph3P)4 PdII
N
N
N
N
PdII (PPh3)4
Cl
NH
KO-t-Bu
O
N
R
KCl
O
(Ph3P)4 PdII
N
N
Bu-t-OH
O-t-Bu
NH2
O
N
O
R = H (9a), o-CF3 (9b), p-OCH3 (9c), o-OCH3 (9d), p-Cl (9e), p-F (9f), p-Br (9g), p-NO2 (9h).
Treatment of the latter with 2-chloro-3-aryl-1,8-napht-
hyridines (5a–5h) in the presence of a catalytic system
tetrakis(triphenylphosphine)palladium(0) [Pd(PPh3)4]
and KO-t-Bu in toluene under MWI at 200 W, gave the
corresponding 2-{4-[(3-aryl-1,8-naphthyridin-2-yl)-
amino]phenyl}-1H-benzo[de]isoquinoline-1,3(2H)-
diones (9a–9h) of high purity in high yields (69–82%)
within short reaction time (3.5–4.5 min) (Table 1).
Structures of compounds 9 were elucidated from IR,
1H, and 13C NMR, and mass spectra.
The plausible mechanism of formation of com-
pounds 9a–9h (Scheme 2) starts with oxidative
addition of tetrakis(triphenylphosphine) palladium(0)
species to 2-chloro-3-aryl-1,8-naphthyridines 5a–5h
leading to the intermediate organopalladium(II) species.
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784
SAKRAM et al.
Table 2. Antimicrobial activity data of the synthesized compounds 9a–9h
Inhibition zone, mm
gram(+ve) bacteria gram(–ve) bacteria
Staphylococcus Bacillus
Compound no.
Concentration, µg/disc
Klebsiella
Escheria
coli
aureus
subtilis
pneumoniae
9a
100
200
15
20
20
22
11
13
30
31
9b
100
200
20
25
35
40
16
20
19
21
9c
100
200
22
25
15
19
16
20
15
18
9d
100
200
28
31
25
28
17
20
16
21
9e
100
200
18
20
15
18
15
18
11
14
9f
100
200
16
18
22
25
20
21
28
30
9g
9h
100
200
11
16
16
18
33
35
20
22
100
200
28
32
31
32
12
15
15
18
Chloramphenicol
100
200
35
39
38
41
42
45
40
44
Alternatively, the same process under conventional
conditions of heating to 90°C in a water bath
completed in 10 h gave compound 9a with the yield
only 42%.
against Bacillus subtilis, Staphylococcus aureus (Gram
+ve) and Escheria coli, Klebsiella pneumoniae (Gram
–ve) at 100 and 200 µg/disc concentration using
chloramphenicol as a reference drug. The accumulated
data demonstrated high activity of the products
(Table 2). The compounds 9c and 9d containing the
electron-donating substituents in phenyl ring (p-OCH3,
o-OCH3), exhibited maximum zones of inhibition
close to that of chloramphenicol. All other compounds
with substituent R = Cl, F, Br in the phenyl ring were
of moderate antibacterial activity. Among all products
the compound 9b exhibited the highest antimicrobial
activity against Bacillus subtilis at a concentration of
20 0 µg/disc.
Antibacterial activity. All synthesized compounds
9a–9h were screened for their antimicrobial activities
His228
Ser225
Asn253
Tyr137
Gly125
Phe256
Phe24
Thr26
Molecular modeling. In this study, the synthesized
ligands have been identified as potent antibacterial
inhibitors. AutoDock4.2 uses binding free energy
assessment to assign the best binding conformation.
Experimental activities and predicted by Lamarckian
Genetic Algorithm dockings values for selected
compounds are summarized in Table 3. With only one
exception the molecules demonstrated interactions and
Leu11
Thr10
Leu28
Fig. 2. Molecular docking interactions of 2-{4-[(3-(2-
trifluoromethyl)phenyl)-1,8-naphthyridin-2-yl)amino]-
phenyl}-1H-benzo[de]isoquinoline-1,3(2H)-dione (9b).
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 4 2018

AN EFFICIENT MICROWAVE-ASSISTED SYNTHESIS
785
Table 3. Molecular docking interactions and their binding energy of 9b, 9d, and 9f
Ligand
no.
Interacting amino
acids
Interacting
residue
Binding energy
ΔG, kcal/mol
Dissociation
constant K, nM
Grid x, y, z coordinates
9b
9d
9f
His228
O–HD1
20.204, 26.232, –0.054
20.204, 26.232, –0.054
20.204, 26.232, –0.054
–9.12
–9.32
207.68
–
–
–
–
146.66
–11.06
7.85
low free energy values, indicating substantial thermo-
dynamic interactions.
2-{4-[(3-Phenyl-1,8-naphthyridin-2-yl)amino]-
phenyl}-1H-benzo[de]isoquinoline-1,3(2H)-dione (9a).
Gray solid, yield 82%, mp 222–224°C. FT-IR spectrum,
ν, cm–1: 3523, 3028, 3307, 1604, 1516, 1354. 1H NMR
spectrum, δ, ppm: 10.12 s (1H), 8.54–8.48 m (5H),
8.17 d (J = 7.7 Hz, 1H), 8.13 s (1H), 7.91 t (J = 7.7 Hz,
2H), 7.77–7.67 m (4H), 7.50–7.37 m (3H), 7.33–7.24
m (3H). 13C NMR spectrum, δ, ppm: 168.4 (2C), 163.7,
161.8, 150.2, 149.2, 139.0 (2C), 136.4 (2C), 135.7, 134.3,
132.6, 131.4, 130.7, 129.2 (2C), 128.7 (2C), 128.0, 127.9
(2C), 127.7 (2C), 127.2 (2C), 122.5 (2C), 119.2, 118.4
(2C), 114.6. MS (EI, m/z, %): 493 [M + H]+. Found, %: C
77.85; H 4.08; N 11.18. C32H20N4O2. Calculated, %: C
78.03; H 4.09; N 11.38.
Docking of the synthesized compounds into the
binding site of a 4M7X and estimating the binding
affinity of the complex was significant for the structure
based drug design process. The structural interactions
between PDB and 3 inhibitors were docked separately.
(x, y, z) Coordinates of PDB were selected by using
SPDBV. The amino acid residues present in the
binding pockets were Thr99, Gly9, Gly125, Gly121,
Thr10, Lys13, Leu11, and Ser225 (Fig. 2).
EXPERIMENTAL
All reagents were used as purchased from Aldrich
Chemical Company. Melting points were measured in
open capillary tubes on a Cintex apparatus and were
uncorrected. Purity of compounds was tested by TLC
using ethyl acetate : n-hexane (2 : 8) as an eluent. IR
spectra were recorded on a Perkin-Elmer spectrum BX
2-{4-[(3-(2-Trifluoromethylphenyl)-1,8-napht-
hyridin-2-yl)amino]phenyl}-1H-benzo[de]isoquino-
line-1,3(2H)-dione (9b). Colorless solid, yield 80%,
mp 250–252°C. FT-IR spectrum, ν, cm–1: 3309, 1705,
1
1656, 1519, 1234, 1111. H NMR spectrum, δ, ppm:
1
series FT-IR spectrophotometer using KBr discs. H
10.13 s (1H), 8.51 s (5H), 8.16 s (1H), 8.01–7.58 m
(8H), 7.48 s (1H), 7.30 s (3H). 13C NMR spectrum, δ,
ppm: 163.7 (2C), 161.8, 150.7, 150.6, 149.6, 139.0,
137.3 (2C), 136.6, 135.5, 134.4 (2C), 133.1, 132.6,
132.1, 131.4, 130.7, 129.2 (2C), 128.6, 127.7, 127.2
(4C), 122.6 (2C), 119.2, 118.8, 118.5 (2C), 113.9. MS
(EI, m/z, %): 561 [M + H]+. Found, %: C 70.51; H
3.16; N 9.85. C33H19F3N4O2. Calculated, %: C 70.71;
H 3.42; N 10.00.
and 13C NMR spectra were measured in CDCl3 or
DMSO-d6 media on a Varian Gemini 400 MHz or 101
MHz spectrometer using TMS as an internal standard.
Mass spectra were measured on a Jeol JMSD-300
spectrometer. Microanalysis was performed on a Carlo-
Erba model EA1108 analytical unit. Irradiation was
carried out in a domestic microwave oven.
The Buchwald–Hartwig amination coupling,
synthesis of 2-{4-[(3-aryl-1,8-naphthyridin-2-yl)amino]-
phenyl}-1H-benzo[de]isoquinoline-1,3(2H)-diones
(9a–9h). Mixture of a compound 5a–5h (1.0 mmol)
with 2-(4-aminophenyl)-1H-benzo[de]isoquinoline-1,3(2H)-
dione 8 (0.288 g, 1.0 mmol), KO-t-Bu (0.170 g,
1.5 mmol), and [Pd0(PPh3)4] (0.578 g, 0.5 mmol) in
toluene (5 mL) was subjected to microwave irradiation
at 200 W intermittently at 30 s intervals for a certain
time (3.5–4.5 min, Table 1). After completion of the
reaction, as indicated by TLC, the mixture was poured
into cool water. The precipitated solid was collected,
washed with n-hexane, dried, and recrystallized from
methanol (3 mL) to give the target compound 9a–9h.
2-{4-[(3-(4-Methoxyphenyl)-1,8-naphthyridin-2-
yl)amino]phenyl}-1H-benzo[de]isoquinoline-1,3(2H)-
dione (9c). Yellow solid, yield 76%, mp 201–203°C. FT-
IR spectrum, ν, cm–1: 3523, 3309, 1703, 1658, 1232,
1
1109. H NMR spectrum, δ, ppm: 12.29 s (1H), 8.54–
8.48 m (2H), 8.21–8.13 m (4H), 8.08 s (1H), 7.90 d
(J = 2.2 Hz, 1H), 7.79–7.70 m (4H), 7.30– 7.22 m
(4H), 7.02 d (J = 9.0 Hz, 2H), 3.81 s (3H). 13C NMR
spectrum, δ, ppm: 163.7, 158.0 (2C), 155.7, 153.8,
151.4, 144.2, 141.9, 141.5, 139.0 (2C), 134.4, 131.4,
130.7, 129.4 (2C), 129.3 (2C), 129.2, 127.8, 129.2,
127.8, 127.2 (2C), 122.5 (2C), 120.0, 119.2, 117.3
(2C), 115.0, 114.2 (2C), 57.1. MS (EI, m/z, %): 523
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 4 2018

786
SAKRAM et al.
[M + H]+. Found, %: C 76.05; H 4.43; N 11.02.
C33H22N4O3. Calculated, %: C 75.85; H 4.24; N 10.72.
2-{4-[(3-(4-Bromophenyl)-1,8-naphthyridin-2-yl)-
amino]phenyl}-1H-benzo[de]isoquinoline-1,3(2H)-
dione (9g). Pale yellow solid, yield 69%, mp 218–220°C.
FT-IR spectrum, ν, cm–1: 3522, 3030, 1660, 1587, 831,
2-{4-[(3-(2-Methoxyphenyl)-1,8-naphthyridin-2-
yl)amino]phenyl}-1H-benzo[de]isoquinoline-1,3(2H)-
dione (9d). Gray solid, yield 69%, mp 200–202°C. FT-
IR spectrum, ν, cm–1: 3522, 3307, 1639, 1182, 1026.
1H NMR spectrum, δ, ppm: 10.67 s (1H), 8.69–8.60 m
(3H), 8.27 t (J = 7.2 Hz, 1H), 7.98–7.92 m (2H), 7.84–
7.76 m (4H), 7.73 d (J = 8.7 Hz, 3H), 7.24–7.19 m
(1H), 7.09 d (J = 8.5 Hz, 1H), 7.03–6.97 m (2H), 6.83
d (J = 8.5 Hz, 1H), 3.87 s (3H). 13C NMR spectrum, δ,
ppm: 163.8 (2C), 163.7, 150.1, 149.8, 139.0, 136.4
(2C), 136.1, 135.9, 135.0, 134.3, 134.2, 131.4, 130.7,
130.6, 129.9, 129.4 (2C), 129.2, 128.7 (2C), 127.2
(2C), 122.6, 122.5 (2C), 119.2 (2C), 118.3, 114.7,
113.4, 56.1. MS (EI, m/z, %): 523 [M + H]+. Found, %:
C 76.15; H 4.54; N 11.00. C33H22N4O3. Calculated, %:
C 75.85; H 4.24; N 10.72.
1
777. H NMR spectrum, δ, ppm): 10.41 s (1H), 8.65 d
(J = 7.7 Hz, 3H), 8.28 t (J = 7.7 Hz, 2H), 7.96 d (J =
9.0 Hz, 1H), 7.76–7.85 m (3H), 7.71 d (J = 8.2 Hz,
1H), 7.56–7.67 m (4H), 7.51 d (J = 10.7 Hz, 1H), 7.38
d (J = 8.0 Hz, 1H), 7.08 d (J = 8.2 Hz, 1H), 6.83 d (J =
13
8.5 Hz, 1H). C NMR spectrum, δ, ppm): 163.7 (2C),
150.5, 149.2, 136.7 (2C), 136.6 (2C), 134.3, 131.4,
131.0, 130.9, 130.8 (2C), 130.7, 130.6 (2C), 129.2,
129.1 (2C), 127.2, 122.7 (2C), 122.5 (2C), 121.4,
120.7, 119.2, 118.5 (2C), 114.5, 113.9. MS (EI, m/z,
%): 571 [M + H]+. Found, %: C 67.51; H 3.43; N
10.02. C32H19BrN4O2. Calculated, %: C 67.26; H 3.35;
N 9.80.
2-{4-[(3-(4-Nitrophenyl)-1,8-naphthyridin-2-yl)
amino]phenyl}-1H-benzo[de]isoquinoline-1,3(2H)-
dione (9h). Brownish yellow solid, yield 78%, mp 240–
242°C. FT-IR spectrum, ν, cm–1: 3522, 3359, 1701,
2-{4-[(3-(4-Chlorophenyl)-1,8-naphthyridin-2-yl)-
amino]phenyl}-1H-benzo[de]isoquinoline-1,3(2H)-
dione (9e). Gray solid, yield 81%, mp 229–231°C. FT-
IR spectrum, ν, cm–1: 3601, 3309, 1662, 1587, 1429,
1
1664, 1512, 1406, 1352. H NMR spectrum, δ, ppm:
10.12 s (1H), 8.61– 8.45 m (6H), 8.38–8.29 m (1H),
8.25–8.15 m (1H), 8.06 d (J = 8.7 Hz, 1H), 7.91 t (J =
7.7 Hz, 3H), 7.70 d (J = 8.7 Hz, 3H), 7.29 d (J =
8.7 Hz, 3H). 13C NMR spectrum, δ, ppm: 168.4 (2C),
163.7, 156.6, 154.9, 150.3, 139.0 (2C), 136.2 (2C),
135.4, 134.7, 134.3, 130.7, 130.5 (2C), 129.2 (2C),
128.6 (2C), 127.7, 127.2 (2C), 122.5, 121.3 (2C), 121.0,
119.2, 116.6 (2C), 114.7, 113.8. MS (EI, m/z, %): 538
[M + H]+. Found, %: C 71.85; H 3.72; N 13.26.
C32H19N5O4. Calculated, %: C 71.50; H 3.56; N 13.03.
1
775, 702. H NMR spectrum, δ, ppm: 10.77 s (1H),
8.68–8.63 m (2H), 8.28 d (J = 8.7 Hz, 1H), 7.97 d (J =
7.7 Hz, 1H), 7.85–7.82 m (2H), 7.79 d (J = 8.0 Hz,
1H), 7.71 d (J = 8.5 Hz, 4H), 7.44 d (J = 8.5 Hz, 3H),
7.30–7.27 m (2H), 7.25–7.21 m (2H). 13C NMR
spectrum, δ, ppm: 168.4 (2C), 163.7, 161.6, 150.4,
149.8, 146.2, 141.4, 139.0, 136.7 (2C), 136.6 (2C),
134.3, 132.7, 131.4, 130.7, 130.5 (2C), 129.2 (2C),
128.0 (2C), 127.7, 127.2 (2C), 122.5 (2C), 119.2,
118.5 (2C), 114.5. MS (EI, m/z, %): 527 [M + H]+.
Found C 73.16; H 3.82; N 10.95. C32H19ClN4O2.
Calculated, %: C 72.93; H 3.63; N 10.63.
Antimicrobial assay. Screening of antimicrobial
activity was carried out by the agar well diffusion
method. The tested organisms were sub cultured on LB
Broth (Lennox) Powder. LB Broth (Lennox) Powder
(1 µL) was dissolved in 10 mL of distilled water in a
test tube and autoclaved at 15 pound pressure for
15 min and cooled. Bacterial culture (10 µL) was
added to the broth in laminar air flow and stored at 4°C
in a refrigerator to maintain the stock.
2-{4-[(3-(4-Fluorophenyl)-1,8-naphthyridin-2-yl)-
amino]phenyl}-1H-benzo[de]isoquinoline-1,3(2H)-
dione (9f). Light yellow solid, yield 80%, mp 238–
240°C. FT-IR spectrum, ν, cm–1: 3523, 3307, 1665,
1
1232. H NMR spectrum, δ, ppm: 10.38 s (1H), 8.68–
8.61 m (3H), 8.31–8.25 m (2H), 7.98–7.94 m (1H),
7.84–7.69 m (8H), 7.25–7.21 m (1H), 7.12–7.19 m
(3H). 13C NMR spectrum, δ, ppm: 163.7 (2C), 156.2,
155.3, 154.6, 152.6, 151.6, 150.8, 149.5, 146.6, 145.1,
142.9, 139.0 (2C), 136.6 (2C), 136.4 (2C), 134.3,
130.9, 130.7 (2C), 129.2 (2C), 127.7, 127.2 (2C),
122.6 (2C), 119.2 (2C), 114.7. MS (EI, m/z, %):
511 [M + H]+. Found, %: C 75.38; H 3.90; N
11.22. C32H19FN4O2. Calculated, %: C 75.28; H 3.75; N
10.97.
A modified Murray (1995) antimicrobial suscepti-
bility was tested on solid media in petri plates. For
bacterial assay nutrient agar (40 gm/L) was used for
developing surface colony growth. The suspension
culture for bacterial cells growth was carried out by
preparing 2% LB Broth (Lennox) Powder (w/v). All
media prepared were sterilized by autoclaving the
media at 121°C for 20 min. Wells (10 mm diameter ca
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AN EFFICIENT MICROWAVE-ASSISTED SYNTHESIS
787
2 cm) were made in each of these plates using a sterile
cork borer. Stock solution of each compound was
prepared at a concentration of 1 µL/mL. About 100 µL
of different concentrations of compounds were added
by sterile pipette into the wells and allowed to diffuse
at room temperature for 2 h. Control experiments
(positive and negative) comprising inoculums without
compounds were set up. The plates were incubated at
37°C for 18–24 h for bacterial pathogens. The
diameter of the inhibition zone (mm) was measured
and the activity index was also calculated. The
experiments were carried out in triplicates and the
average values were recorded. The minimum
inhibitory concentration was defined as the lowest one.
method MW heating, which is more efficient than the
classical conditions. We determined that compounds
9a–9h demonstrated in vitro antimicrobial potency.
Molecular docking study was carried out.
ACKNOWLEDGMENTS
The authors are thankful to the Directors, CFRD-
1
OU, IICT, Hyderabad for providing IR, H, and 13C
NMR, and mass spectral and analytical data. One of
the author (B. Sakram) expresses thanks to the
University Grant Commission, New-Delhi, India, for
the financial support.
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