S.A. Khan et al.
Bioorganic Chemistry 112 (2021) 104964
Scheme 1. Synthesis of 9-ethyl carbazole-3-carboxaldehyde.
substituted carbazole framework generates an excellent donor-
-acceptor chromophore [7]. Recently, quinoline derivatives with
CH Aromatic, J = 6.8 Hz), 7.63 (dd, 1H, CH Aromatic, J = 5.6, 4.2 Hz),
7.53 (dd, 1H, CH Aromatic, J = 3.4, 4.2 Hz), 7.48 (s, 1H, CH Aromatic),
7.32 (d, 1H, CH Aromatic, J = 7.4 Hz), 7.26 (s, 1H, CH Aromatic), 7.09
(d, 1H, CH Aromatic, J = 7.6 Hz), 6.96 (d, 1H, CH Aromatic, J = 7.4 Hz),
π
excellent photophysical properties, like blue emission and good fluo-
rescence quantum yield, have been reported [8]. Quinoline derivatives
are of continued interest for synthetic organic chemistry as well as
medicinal chemistry [9]. Polysubstituted quinolines are significant
heterocyclic compounds due to their diverse biological activities like
anti-cancer [10], antibacterial [11], anti-HIV [12], antimalarial and
anti-inflammatory [13]. In addition, quinoline derivatives have also
been used in the electronic and optoelectronic field because of their
attractive electrical, optical and mechanical properties [14]. Therefore,
5
.12 (s, 2H, NH
2
), 4.06 (q, 2H, N-CH
), 2.79–2.74 (m, 2H, CH ), 2.68–2.61 (m, 2H, –CH
) δ: 161.43, 158.93,
2
-CH
3
, J = 6.8 Hz), 3.66 (s, 3H, O-
CH
CH
3
3
2
2
), 1.21 (t, 3H,
13
-CH
2
-N, J = 6.2 Hz); C NMR (125 MHz, CDCl
3
1
1
57.20, 154.29, 153.56, 151.24, 149.12, 145.87, 142.92, 128.63,
25.12, 124.96, 123.21, 121.98, 119.34, 116.54, 114.12, 112.96 56.12
(
O-CH
3
), 38.56 (CH
3
-CH
2
2 2 3
-N), 28.28 (CH ), 25.96 (CH ), 16.21 (CH -
CH
2
-N); Anal. Calc. for C29 H N
24 4
O: C, 78.36, H, 5.94, N, 12.60, Found:
we have developed a novel heterocyclic donor- -acceptor chromophore
π
C, 78.31, H, 65.89, N, 12.56.
with promising photophysical characteristics and biological profile with
the integration of the carbazole and quinolines units.
2
2
.4. Antibacterial activity of the heterocyclic chalcone
2
. Experimental
.4.1. Media and strains
The synthesized compound was tested with bacterial strains (Gram-
2
.1. Chemicals and reagents
positive and Gram-negative), namely Staphylococcus aureus (FNCC
047), Bacillus substilis (FNCC 0041), Eschericia coli (FNCC 0091) and
0
Chemical reagents and solvents were obtained from commercial
Shigella flexnerri (ATCC 12022). Nutrient medium (Peptone 5 g/L; beef
sources (Sigma-Aldrich/Merck) and were used as such. For UV–visible
absorption spectra, and fluorescence spectra measurements, HPLC grade
solvents were used. Carbazole-3-carbaldehyde was prepared (Scheme 1)
according to the reported procedure [15].
◦
extract 3 g/L; pH = 7.0) and incubation time 24 h at 37 C was used to
subculture the bacteria.
2
.4.2. Disc-diffusion evaluation
Disc-diffusion technique was applied to evaluate the antibacterial
2
.2. Instrumentation
activity of newly synthesized heterocyclic quinoline-3-carbonitrile
AEDQ). The method was performed as described earlier with insignif-
(
Reaction progress was monitored using pre-coated aluminium sheets
icant alteration [17].
(
Silica gel 60F254) for TLC from Merck. Melting point (m.p.) of the
Briefly, the entire bacterial cells were developed in BHI medium for
◦
5
synthesized compounds was measured in open capillary tubes using
Stuart scientific apparatus. Perkin-Elmer 100FT-IR spectrophotometer
the period of 24 h at 37 C. After incubation, about 10 CFU/ml bacterial
◦
load were inoculated on sterile nutrient agar at 40 C in laminar flow
1
was used to obtain the FTIR spectrum while HNMR (600 MHz) and
hood. On these nutrient agar plates with bacterial strains, paper discs
1
3
CNMR (125 MHz) spectrum of the heterocyclic quinoline-3-
carbonitrile (AEDQ) was recorded in CDCl on Bruker spectrometer.
(diameter = 6.0 mm) treated with 10, 20, 25, 50, 100
μ
g/mL solution of
3
heterocyclic quinoline-3-carbonitrile (AEDQ) in DMSO were applied.
Elementar Analysensysteme GmbH VarioEL elemental analyzer was
employed for the elemental analysis of quinoline-3-carbonitrile. Shi-
madzu UV-16550PC UV–Visible and RF-5301PC was employed to get
the UV–visible and fluorescence spectra of quinoline-3-carbonitrile
DMSO as negative control and tetracycline (30
antibiotic drug was used.
μ
g/mL) as reference
The efficacy of different concentration of heterocyclic quinoline-3-
carbonitrile (AEDQ) on the bacteria was evaluated with the zone of in-
◦
(
AEDQ), respectively.
hibition after incubation period of 24 h at 37 C.
2
.3. Synthesis of 2-Amino-4-(9-ethyl-9H-carbazol-3-yl)-8-methoxy-5,6-
2.4.3. Antibacterial activity by MIC assay
dihydrobenzo[h]quinoline-3-carbonitrile (AEDQ)
Minimum Inhibitory concentration (MIC) was also determined to
evaluate antibacterial efficiecy of the quinoline-3-carbonitrile (AEDQ)
by broth dilution assay. Heterocyclic quinoline-3-carbonitrile (AEDQ)
was dissolved in DMSO, and different concentration (512, 256, 128, 64,
AEDQ was synthesized by the condensation of 6-methoxy-3,4-dihy-
dronaphthalen-1(2H)-one (5.67 mmol, 1.0 g), 9-ethyl-3-carbazole-
carboxaldehyde (5.67 mmol, 1.26 g), malononitrile (5.67 mmol, 0.36 g),
32, 16, 8, 4, 2 and 1 g/mL) of the compound were prepared from the
μ
and NH
normal microwave oven (at 210 W, MW power) for 7 min. TLC (Silica gel
0F254) was used to monitor the progress of the reaction. After com-
4
OAc (5.67 mmol, 2.58 g), in absolute alcohol was heated in
stock solution by serial dilution. These serial dilutions of the heterocy-
clic quinoline-3-carbonitrile (AEDQ) were added in each test tube with
1 mL of bacterial cultures (approximately 105 CFU/ mL) standard
inoculant. The MIC of the heterocyclic quinoline-3-carbonitrile (AEDQ),
6
plete consumption of reactants, ice-water was added to the mixture,
filtered the solid thus obtained, and recrystallized from ethanol [16].
◦
was evaluated after incubation at 37 C for 24 h. DMSO and Tetracycline
ꢀ
1
Orange crystals, %yield: 87.50%; FT-IR (
ν
, cm ): 3432 (NH
2
), 3092
was used as negative and positive controls [18].
(
C-H stretching), 2932 (C-H stretching), 1561 (C = C aromatic stretch-
–
1
ing), 1253 (C
–
N), H NMR (600 MHz CDCl
3
) δ:8.09 (d, 1H, CH Aro-
matic, J = 7.2 Hz), 7.89 (d, 1H, CH Aromatic, J = 8.4 Hz), 7.71 (d, 1H,
2