Design, synthesis and study of antibacterial and antitubercular activity of quinoline hydrazone hybrids

Article abstract of DOI:10.1515/hc-2020-0109

Emerging bacterial resistance is causing widespread problems for the treatment of various infections. Therefore, the search for antimicrobials is a never-ending task. Hydrazones and quinolines possess a wide variety of biological activities. Herewith, eleven quinoline hydrazone derivatives have been designed, synthesized, characterized and evaluated for their antibacterial activity and antitubercular potential against Mtb WT H37Rv. Compounds QH-02, QH-04 and QH-05 were found to be promising compounds with an MIC value of 4 μg/mL against Mtb WT H37Rv. Compounds QH-02, QH-04, QH-05, and QH-11 were also found to be active against bacterial strains including Acinetobacter baumanii, Escherichia coli and Staphylococcus aureus. Further, we have carried out experiments to confirm the cytotoxicity of the active compounds and found them to be non-toxic.

Full text of DOI:10.1515/hc-2020-0109

Heterocycl. Commun. 2020; 26: 137–147
Research Article
Open Access
Shruthi T G, Sangeetha Subramanian* and Sumesh Eswaran
Design, Synthesis and Study of Antibacterial
and Antitubercular Activity of Quinoline
Hydrazone Hybrids
https://doi.org/10.1515/hc-2020-0109
Received May 21, 2020; accepted August 08, 2020.
novel mechanisms of action are necessary to develop novel
therapeutic treatment combinations. Among heterocyclic
compounds, compoundswithaquinolinecorehavegained
much importance in medicinal chemistry. Quinoline
compounds are vital structures in medicinal chemistry
due to their wide spectrum of biological activity, including
anti-inflammatory [2], anticancer [3,4], antihypertensive
Abstract: Emerging bacterial resistance is causing wides-
pread problems for the treatment of various infections.
Therefore, the search for antimicrobials is a never-ending
task. Hydrazones and quinolines possess a wide variety
of biological activities. Herewith, eleven quinoline hyd-
razone derivatives have been designed, synthesized, cha-
racterized and evaluated for their antibacterial activity
and antitubercular potential against Mtb WT H37Rv. Com-
pounds QH-02, QH-04 and QH-05 were found to be pro-
mising compounds with an MIC value of 4 µg/mL against
Mtb WT H37Rv. Compounds QH-02, QH-04, QH-05,
and QH-11 were also found to be active against bacterial
strains including Acinetobacter baumanii, Escherichia coli
and Staphylococcus aureus. Further, we have carried out
experiments to confirm the cytotoxicity of the active com-
pounds and found them to be non-toxic.
[
5], tyrokinase PDGF-RTK-inhibiting [6], anti-HIV [7],
anti-malarial [8,9] and anti-bacterial activity [10,11]. They
are also known to exhibit excellent anti-TB [12,13,14]
properties. For example, Bedaquiline is an important
quinoline-based anti-TB drug for the treatment of MDR-TB
[
15]. Quinoline is also a key component of many naturally-
occurring bioactive compounds.
Hydrazones belong to a class of organic compounds
containing a C = N bond, in which the nitrogen atom is
nucleophilic and the carbon atom has both electrophilic
and nucleophilic character. Owing to their biological and
pharmacological properties, combining hydrazones with
Keywords: Quinoline, Hydrazone, Antituberculosis, other heterocyclic compounds leads to diverse biological
Antibacterial activity, Cytotoxicity
and pharmacological properties.
Quinoline hybrids combine polar and nonpolar
properties, allowing them to permeate bacterial cells.
It is evident from the literature that quinoline-based
hydrazone scaffolds exhibit excellent antibacterial and
anti-TB properties. The quinoline hydrazone derivatives
Introduction
There is an urgent need for the screening of new bioactive synthesized by Eswaran et al. showed better anti-
molecules with new targets and novel mechanisms of tuberculosis potency than rifampin and isoniazid [16],
action to address the emerging problem of antibacterial while new fluorine-substituted hydrazones also exhibited
resistance. There are about 558,000 reported cases good anti-tuberculosis potency [17]. These molecules
of rifampicin-resistant tuberculosis. Further, 82% also showed remarkable anti-cancer properties [18]. The
had multidrug-resistant tuberculosis (MDR-TB), with quinoline hydrazone moiety has tremendously enhanced
maximum incidence in India, China and the Russian the anti-TB activity of these compounds.
Federation [1]. Discovery of novel chemical scaffolds with
We have designed new quinoline derivatives via two
synthetic routes. These are the unique scaffolds with
quinoline, piperazine or morpholine and hydrazones
present in the molecules. The idea to design these two
completely different scaffolds was motivated by a survey of
the literature. The intermediate 7-chloro-4-(piperazin-1-yl)
quinoline (5) is an important building block in medicinal
*
Corresponding author: Sangeetha Subramanian, SBST, Vellore
Institute of Technology, Vellore – 632014, Tamil Nadu, India
E-mail: sangeethasubramanian@vit.ac.in; Tel.:+971501099154
Shruthi T G, Sumesh Eswaran, Anthem Biosciences Pvt, Ltd.,
Bangalore-560099, Karnataka, India
Open Access. © 2020 Shruthi T G et al., published by De Gruyter.ꢀ
Attribution alone 4.0 License.
ꢀThis work is licensed under the Creative Commons

ꢁ
Shruthi T G et al.: Design, Synthesis and Study of Antibacterial and Antitubercular Activity
1
38ꢁ
chemistry, where it is combined with other active triplets; m, multiplet; brs, broad singlet. IR spectra were
pharmacophores with diverse pharmacological profiles recorded using a Bruker Alpha FTIR spectrometer using a
[
19,20,21]. Some 7-chloro-4-(piperazin-1-yl)quinoline- diamond ATR single reflectance module (32 scans).
carrying propionic acid hydrazone derivatives synthesized
by Inam et al. were shown to be effective as antiprotozoal
agents [22]. Hydrazone derivatives of quinoline and their General procedure for the synthesis of compounds
Zn(II) complexes, synthesized by Mandewale, M. C. et al.,
were good antitubercular agents [23] and the 7-chloro-4- Preparation of 2-[(3-chloro-phenylamino)-methylene]-
quinolinylhydrazone derivatives synthesized by Candea malonic acid diethyl ester (2)
et al. exhibited significant activity comparable with that
of the first line drugs, ethambutol and rifampicin [24]. A suspension of 3-chloro-phenylamine (1) 50 g (0.391 mol.)
This evidence inspired us to design scaffold 1. 4-hydroxy- in diethyl ethoxymethylenemalonate 119 mL (0.587 mol.)
8
-trifluoromethyl-quinoline derivatives were synthesized was heated at 110 °C for 4 h. The reaction mixture was
and screened for in vitro anti-TB activity against various cooled to room temperature, the solid formed was
strains of Mycobacterium by Thomas et al. [25]. The mode placed in hexane (10 vol.), stirred for 15 min and filtered
of action of these active compounds involved docking of to get compound (2) as a pale yellow solid. The isolated
receptor enoyl-ACP reductase with the newly synthesized compound was used in the next step without further
candidate ligands. This encouraged us to design scaffold 2. purification. Yield: 70 g (60 %)
The overall strategy is to attach hydrazones at the second
and fourth positions of the quinoline ring and to screen
for resulting antimicrobial activity.
In the present work, all new structures were designed
on the basis of combinatorial synthesis, keeping structure-
Preparation of 7-chloro-4-hydroxyquinoline (3)
solution of 2-[(3-chloro-phenylamino)-methylene]-
A
activityrelationshipstudiesinmindinlinewiththecurrent malonic acid diethyl ester (2) 50 g (0.168 mol.) in Dowtherm
trend in drug discovery. All compounds were characterized medium (100 mL, 2 vol.) was heated at 240 °C for 4 h. The
by NMR spectra as well as mass spectroscopy. Amongst reaction mixture was cooled to room temperature. Hexane
the tested compounds, QH-02, QH-04, QH-05 and QH-11 was added and the mixture was stirred for 15 min, after
displayed promising antimicrobial activity.
which the solid precipitate was filtered and dried to get
compound (3) as an off-white solid. Yield: 15 g (49.7 %)
1
H-NMR (CDCl3 400 MHz) δ (ppm): 6.05 (d, 1H,
J = 7.6 Hz, ArH), 7.32 (dd, 1H, J = 8.8, 2 Hz, ArH), 7.58 (d, 1H,
J = 2 Hz, ArH), 7.93 (t, 1H, J = 7.2 Hz, ArH), 8.07 (d, 1H, J = 8.8
Experimental
Chemistry
1
3
Hz, ArH), 11.78 (brs, 1H, -OH). C-NMR (DMSO 100 MHz) δ
(ppm): 109.76, 117.90, 123.92, 124.81, 127.75, 136.71, 140.48,
-1
1
41.26, 176.77. IR (KBr) cm : 3065, 2944, 1608, 1559, 814. LC/
All reagents were purchased from Sigma Aldrich. Solvents MS (ESI-MS) m/z = 180 (M+1).
used were extra dried. Final purifications were carried
out using a Quad Biotage Flash purifier (A Dyax Corp.
Company). TLC experiments were performed on alumina- Preparation of 4,7-dichloro-quinoline [26] (4)
backed silica gel 40 F254 plates (Merck, Darmstadt,
Germany). The plates were illuminated under UV A phosphorus oxychloride (10 mL, 1 vol.) was added to
1
13
(
254 nm) and KMnO . All H and C NMR spectra were 7-chloro-4-hydroxyquinoline (3) (10 g, 0.055 mol.) in a
4
recorded on a Bruker AM-300 (300.12 MHz) and AM-400 round bottom flask equipped with a reflux condenser.
400.13 MHz) (Bruker BioSpin Corp., Germany). Molecular The mixture was heated to reflux for 6 h, then allowed to
weights of unknown compounds were checked by LCMS cool to room temperature. The solution was concentrated
200 series Agilent Technology. The mass spectra of a under high vacuum to a thick oil, then dumped over
(
6
few were recorded in a 410 Prostar binary PDA detector cracked ice. The resulting solution was neutralized with
(
Varian Inc., USA). Chemical shifts are reported in ppm saturated NaHCO (aq.), and the solid precipitated was
3
(
δ) with reference to internal standard TMS. The signals filtered and washed with water. The solid was dried under
are designated as follows: s, singlet; d, doublet; t, triplet; vacuum and the crude compound was purified by column
dd, doublet of doublets; td, triplet of doublets; tt, triplet of chromatography over silica gel using eluent 30 % ethyl

Shruthi T G et al.: Design, Synthesis and Study of Antibacterial and Antitubercular Activityꢁ
ꢁ139
acetate in hexane to afford 4,7-dichloroquinoline as a 1.5 N HCl (pH~6). It was concentrated to remove organic
white solid. Yield: 8 g (72.7 %)
H-NMR (DMSO 400 MHz) δ (ppm): 7.79-7.82 (m, 2H, with ethyl acetate (100 mL x 2). The combined organic
ArH), 8.18 (d, 1H, J = 2 Hz, ArH), 8.23 (d, 1H, J = 8.8 Hz, layerwasdriedoversodiumsulphate, filteredandconcen-
ArH), 8.88 (d, 1H, J = 4.8 Hz, ArH). C-NMR (DMSO 100 trated under vacuum to afford a pale yellow solid. Yield:
MHz) δ (ppm): 122.42, 124.62, 126.11, 128.53, 129.02, 135.77, 10 g (49.2%)
solvents and the resultant aqueous layer was extracted
1
13
-1
1H-NMR (DMSO 400 MHz) δ (ppm): 4.60 (d, 2H), 5.76
(s, 1H, -OH), 7.53 (d, 2H, J = 8 Hz), 7.87 (d, 2H, J = 8 Hz), 9.98
1
41.70, 149.18, 152.24. IR (KBr) cm : 3433, 1606, 1608, 1553,
1
485, 817. LC/MS (ESI-MS) m/z = 198 (M+1)
(
s, 1H, -CHO)
Preparation of 7-chloro-4-piperazin-1-yl-quinoline [26] (5)
Preparation of 4-chloromethyl-benzaldehyde (5c)
To a suspension of 4,7-dichloro-quinoline (4) (50 g, 0.252
mol.) in isopropyl alcohol (150 mL, 3 vol.) was added A solution of 4-(hydroxymethyl) benzaldehyde (5b) (10 g,
piperazine (65.2 g, 0.757 mol.) at ambient temperature. 0.073 mol.) in toluene (100 mL, 10 vol.) was cooled to 0 °C.
The reaction mixture was stirred under nitrogen at Thionyl chloride (8 mL, 0.110 mol.) was added dropwise,
9
0 °C for 16 h. The reaction mass became a clear solution followed by 2 drops of DMF. The resultant mixture was
at the beginning and slow precipitation of the solid was stirred at ambient temperature for 16 h and the progress of
observed. The progress of the reaction was monitored the reaction was monitored by TLC analysis. The reaction
by TLC analysis. The reaction mass was cooled to mixture was quenched with ice cold water and basified
room temperature and diluted with ethyl acetate (1 L, with aqueous sodium bicarbonate solution to attain
2
0 vol.). The unreacted piperazine was precipitated and pH=8. The aqueous layer was extracted with ethyl acetate
removed by filtration. The filtrated solid was washed (100 mL x 2). The combined organic layer was dried over
with ethyl acetate (500 mL). The filtrate was washed sodium sulphate filtered and concentrated under vacuum
with water (500 mL x 2), dried over sodium sulphate to afford crude compound. This was purified by column
and concentrated under reduced pressure to give the chromatography over silica gel using eluent 20 % ethyl
desired crude compound. The crude compound was acetate in hexane. Yield: 7 g (62%)
1
purified by column chromatography using silica gel
H-NMR (CDCl , 400 MHz) δ (ppm): 4.65 (s, 2H), 7.57
3
(
60-120), eluent 5 % methanol in dichloromethane to (d, 2H, J = 8 Hz), 7.89 (d, 2H, J = 8 Hz), 10.03 (s, 1H, -CHO)
get the desired compound as a pale yellow solid. Yield:
5
0 g (80.0 %)
1
H-NMR (DMSO 400 MHz) δ (ppm): 2.94 (brs, 4H, -CH ), Preparation of 4-[4-(7-chloro-quinolin-4-yl)-piperazin-1-
.06 (brs, 4H, -CH ), 6.97 (d, 1H, J = 4.8 Hz, ArH), 7.53 (dd, ylmethyl]-benzaldehyde (6)
2
3
1
1
(
1
2
H, J = 8.8, 2.4 Hz, ArH), 7.96 (d, 1H, J = 2 Hz, ArH), 8.00 (d,
13
H, J = 8.8 Hz, ArH), 8.68 (d, 1H, J = 4.8 Hz, ArH). C-NMR To a solution of 7-chloro-4-(piperazin-1-yl) quinoline HCl
DMSO 100 MHz) δ (ppm): 45.99, 53.68, 109.67, 121.88, salt (5) (5 g, 0.017 mol.) in a mixture of acetonitrile (50 mL,
26.04, 126.53, 128.53, 133.94, 150.15, 152.63, 157.34. IR (KBr) 10 vol.) and DMF (50 mL, 10 vol.) was added triethyl amine
-1
cm : 3254, 2942, 2824, 1567, 865, 822. LC/MS (ESI-MS) (7.2 mL, 3 eq.) followed by 4-chloromethyl-benzaldehyde
ο
m/z = 248 (M+1)
(3.26 g, 0.21 mol.) at 0 C. The resultant mixture was
stirred at ambient temperature for 30 h. The progress of
the reaction was monitored by TLC analysis. The reaction
mixture was diluted with ice cold water (200 mL) with
stirring. The white solid precipitated was filtered and
Preparation of 4-hydroxymethyl-benzaldehyde (5b)
A solution of terephthalaldehyde (5a) (20 g, 0.149 mol.) dried under high vacuum to afford the desired compound.
in a mixture of ethanol (200 mL, 10 vol.) and THF Yield: 5 g (77.6 %)
(
240mL,12vol.)wascooledto0±5°C.Totheabovemixture
1H-NMR (DMSO 400 MHz) δ (ppm): 2.68 (brs, 4H), 3.20
sodium borohydride (2.25 g, 0.059 mol.) was added in (brs, 4H), 3.71 (s, 2H), 7.00 (d, 1H, J = 5.2 Hz), 7.55 (dd, 1H,
two lots with stirring at 0 °C for 2 h. The reaction progress J = 8.8, 2 Hz), 7.60 (d, 2H, J = 8 Hz), 7.90 (d, 2H, J = 8 Hz),
was monitored by TLC analysis. The reaction mixture 7.94 (dd, 2H, J = 8, 2 Hz), 8.70 (d, 1H, J = 5.2 Hz), 10.0 (s, 1H,
was quenched with ice cold water and acidified with -CHO). LC/MS (ESI-MS) m/z = 366 (M+1)

ꢁ
Shruthi T G et al.: Design, Synthesis and Study of Antibacterial and Antitubercular Activity
1
40ꢁ
General procedure for preparation of N-[1-{4-[4-(7-
chloro-quinolin-4-yl)-piperazin-1-ylmethyl]-phenyl}-
methylidene]-N’-aryl-hydrazine (QH-01 to QH-05)
Preparation of N-[1-{4-[4-(7-chloro-quinolin-4-yl)-
piperazin-1-ylmethyl]-phenyl}-methylidene]-N’-(4-
methoxy-phenyl)-hydrazine (QH-03)
To a solution of 4-[4-(7-chloro-quinolin-4-yl)-piperazin- This compound was prepared by reacting 4-[4-(7-chloro-
1
-ylmethyl]-benzaldehyde (6) (500 mg, 1.366 mmol.) in quinolin-4-yl)-piperazin-1-ylmethyl]-benzaldehyde
(6)
ethanol (5 mL, 10 vol.) was added hydrazine hydrochloride (500 mg, 1.366 mmol.) with 4-methoxyphenylhydrazine
ο
derivative (1.933 mmol.) at 0 C. The resultant mixture hydrochloride (337 mg, 1.933 mmol.). Yield: 0.3 g (45.2%)
1
was stirred at ambient temperature for 3 h. The reaction
H NMR (CD OD 400 MHz) δ (ppm): 3.25 (brs, 4H, -CH ),
3
2
progress was checked by TLC analysis. The reaction 3.60 (brs, 4H, -CH ), 3.75 (s, 3H, -CH ), 4.13 (s, 2H, -CH ),
2
3
2
mixture was diluted with ice cold water (20 mL), solid 6.84 (d, 2H, J = 8.8 Hz, ArH), 7.04 (d, 2H, J = 8.8 Hz, ArH),
precipitated was filtered and dried under high vacuum to 7.12 (d, 1H, J = 5.6 Hz, ArH), 7.48 (d, 2H, J = 8 Hz, ArH), 7.36
afford desired compound.
(dd, 1H, J = 9.2, 2 Hz, ArH), 7.7 (d, 2H, J = 8 Hz, ArH), 7.75
s, 1H, ArH), 7.96 (s, 1H, ArH), 8.13 (d, 1H, J = 8.8 Hz, ArH),
.65 (d, 1H, J = 5.6 Hz, ArH)
(
8
Preparation of 3-{N’-[1-{4-[4-(7-chloro-quinolin-4-yl)-
piperazin-1-ylmethyl]-phenyl}-methylidene]-hydrazino}-
benzonitrile (QH-01)
1
3
C NMR (DMSO, 100 MHz) δ (ppm): 48.83, 50.59, 55.26,
8.93, 109.35, 113.09, 114.61, 120.66, 125.39, 126.14, 126.23,
26.97, 129.59, 131.50, 134.36, 136.18, 148.27, 150.92, 152.72,
55.70. LC/MS (ESI-MS) m/z = 486.02 (M+1)
5
1
1
This compound was prepared by reacting 4-[4-(7-chloro-
quinolin-4-yl)-piperazin-1-ylmethyl]-benzaldehyde
(6)
(
500 mg, 1.366 mmol.) with 3-cyanophenylhydrazine
Preparation of N-[1-{4-[4-(7-chloro-quinolin-4-yl)-
piperazin-1-ylmethyl]-phenyl}-methylidene]-N’-p-tolyl-
hydrazine (QH-04)
hydrochloride (327 mg, 1.933 mmol.). Yield: 0.3 g (45.66%)
1
H-NMR (D O 400 MHz) δ (ppm): 3.33 (brs, 4H, -CH ),
2
2
3
.47 (brs, 4H, -CH ), 4.29 (s, 2H, -CH ), 7.09 (d, 1H, J = 5.2 Hz),
2
2
7
.16 (d, 1H, J = 7.6 Hz), 7.31 (d, 1H, J = 1.2 Hz), 7.38-7.42 (m, 2H,
This compound was prepared by reacting 4-[4-(7-chloro-
ArH), 7.31-7.43 (m, 3H, ArH), 7.76 (d, 2H, J = 8 Hz, ArH), 7.94
quinolin-4-yl)-piperazin-1-ylmethyl]-benzaldehyde
(6)
(
(
s, 1H, ArH), 7.99 (s, 1H, ArH), 8.06 (d, 1H, J = 9.2 Hz), 8.69
d, 1H, J = 5.2 Hz)
(
(
500mg, 1.366mmol.)withp-tolylhydrazinehydrochloride
306 mg, 1.933 mmol.). Yield: 0.36 g (56%)
13C-NMR (DMSO, 100 MHz) δ (ppm): 48.23, 49.99,
1
H NMR (CD OD 400 MHz) δ (ppm): 2.24 (s, 3H, -CH ),
3
3
5
8.38, 107.86, 111.92, 114.37, 116.79, 118.85, 119.23, 121.94,
3
6
.30 (brs, 4H, -CH ), 3.61 (brs, 4H, -CH ), 4.18 (s, 2H, -CH ),
2
2
2
1
1
=
22.10, 126.17, 127.70, 129.48, 130.40, 131.91, 136.47, 136.77,
37.61, 142.66, 145.64, 145.81, 158.75. LC/MS (ESI-MS) m/z
.98 (d, 2H, J = 8.4 Hz, ArH), 7.03 (d, 2H, J = 8.8 Hz, ArH),
7.12 (d, 1H, J = 5.6 Hz, ArH), 7.52 (d, 2H, J = 8 Hz, ArH), 7.58
481.6 (M+1)
(
(
dd, 1H, J = 8.2, 2 Hz, ArH), 7.7 (d, 2H, J = 8 Hz, ArH), 7.75
s, 1H, ArH), 7.96 (s, 1H, ArH), 8.12 (d, 1H, J = 8.8 Hz, ArH),
Preparation of N-[1-{4-[4-(7-chloro-quinolin-4-yl)-
piperazin-1-ylmethyl]-phenyl}-methylidene]-N’-(4-
fluoro-phenyl)-hydrazine (QH-02)
8.64 (d, 1H, J = 5.6 Hz, ArH)
1
3
C NMR (DMSO, 100 MHz) δ (ppm): 24.18, 48.41, 50.22,
58.58, 108.62, 112.13, 119.72, 124.36, 125.56, 126.54, 126.85,
27.04, 131.83, 134.72, 135.65, 137.15, 138.97, 143.16, 145.50,
This compound was prepared by reacting 4-[4-(7-chloro- 148.50, 157.27. LC/MS (ESI-MS) m/z = 470.5 (M+1)
quinolin-4-yl)-piperazin-1-ylmethyl]-benzaldehyde (6)
1
(
500 mg, 1.366 mmol.) with 4-fluorophenylhydrazine
hydrochloride (314 mg, 1.933 mmol.). Yield: 0.35 g (54%)
Preparation of N-[1-{4-[4-(7-chloro-quinolin-4-yl)-
1
H NMR (DMSO 400 MHz) δ (ppm): 3.84 (brs, 4H, piperazin-1-ylmethyl]-phenyl}-methylidene]-N’-
CH ), 4.14 (brs, 4H, -CH ), 4.42 (s, 2H, -CH ), 7.08 (s, 4H, (4-isopropyl-pheny)-hydrazine (QH-05)
-
2
2
2
ArH), 7.31 (d, 1H, J = 6.4 Hz, ArH), 7.64 (d, 2H, J = 8 Hz), 7.74-
7
.70 (m, 3H, ArH), 7.89 (s, 1H, ArH), 8.1 (dd, 2H, J = 8, 4.4 This compound was prepared by reacting 4-[4-(7-chloro-
Hz, ArH), 8.84 (d, 1H, J = 6.4 Hz, ArH), 10.55 (s, 1H, -NH), quinolin-4-yl)-piperazin-1-ylmethyl]-benzaldehyde (6)
1
3
C NMR (DMSO, 100 MHz) δ (ppm): 48.91, 50.68, 58.97, (500 mg, 1.366 mmol.) with 4-isopropylphenylhydrazine
1
1
1
09.43, 113.03, 115.64, 120.71, 125.69, 126.19, 126.28, 127.06, hydrochloride (360 mg, 1.933 mmol). Yield; 0.35 g (51.4%)
1
31.53, 134.33, 135.57, 136.65, 141.85, 148.35, 150.99, 154.82,
55.71, 157.14. LC/MS (ESI-MS) m/z = 474.5 (M+1)
H NMR (CD OD 400 MHz) δ (ppm): 1.22 (d, 6H, -CH3),
3
2.82(sept, 1H, -CH), 3.49(brs, 4H, -CH ), 3.86(brs, 4H, -CH ),
2
2

Shruthi T G et al.: Design, Synthesis and Study of Antibacterial and Antitubercular Activityꢁ
ꢁ141
4
.37 (s, 2H, -CH ), 7.02 (d, 2H, J = 8.4 Hz, ArH), 7.09 (d, 2H, added morpholine (21 mL, 0.244 mol.). This was heated
2
J = 8.4 Hz, ArH), 7.23 (d, 1H, J = 6.4 Hz, ArH), 7.57 (d, 2H, with stirring at 90 °C for 30 h. The reaction was monitored
J = 8 Hz, ArH), 7.75-7.67 (m, 4H, ArH), 8.00 (s, 1H, ArH), 8.17 by TLC analysis. The reaction mixture was cooled to room
(
d, 1H, J = 9.2 Hz, ArH), 8.68 (d, 1H, J= 6.4 Hz, ArH)
temperature and concentrated to dryness. The crude
13
C NMR (DMSO, 100 MHz) δ (ppm): 24.18, 32.67, 48.41, compound was diluted with water (200 mL, 10 vol.)
5
0.22, 58.58, 108.62, 112.13, 119.12, 124.36, 125.56, 126.54, and extracted with dichloromethane (100 mL x 2). The
1
1
26.85, 127.04, 131.83, 134.72, 135.15, 137.15, 138.97, 143.16, combined organic layer was dried over sodium sulphate,
57.27. LC/MS (ESI-MS) m/z = 498.08 (M+1) filtered and concentrated under reduced pressure at
0-45 °C to yield the crude product as a brown solid. It
4
was purified by flash chromatography using 80 % ethyl
acetate in hexane. Yield: 16 g (66.3 %).
Preparation of 2-Methyl-8-trifluoromethyl-quinolin-4-ol (9)
1
H NMR (CDCl , 400 MHz) δ (ppm): 2.74 (s, 3H, -CH ),
3
3
To a solution of 2-trifluoromethyl aniline (8) (25 g, 3.19 (t, 4H, -CH ), 3.99 (t, 4H, -CH ), 6.84 (s, 1H, ArH), 7.46
2
2
0
.155 mol.) and ethyl acetoacetate (25.1 mL, 0.201 mol.) (t, 1H, J = 8.0 Hz, ArH), 7.99 (d, 1H, J = 6.8 Hz, ArH), 8.19 (d,
was added polyphosphoric acid (125 g, 5 w/w), and the 1H, J = 8.4 Hz, ArH)
reaction mixture was stirred at 150 °C for 2 h. The reaction
13C NMR (DMSO, 100 MHz) δ (ppm): 25.55, 52.28, 66.03,
was monitored by TLC. The reaction mixture was slowly 110.30, 121.75, 123.25, 124.21, 125.23, 127.54, 128.56, 145.14,
poured into ice water (500 mL) with vigorous stirring. The 156.37, 160.36. LC/MS (ESI-MS) m/z = 297.5 (M+1)
precipitate solid was filtered, washed with water and dried
under high vacuum at 50 °C to get the desired product as
an off-white solid. Yield: 27 g (76.6%)
Preparation of 4-Morpholin-4-yl-8-trifluoromethyl-
1
H NMR (CDCl , 400 MHz) δ (ppm): 2.49 (s, 3H, -CH ), quinoline-2-carbaldehyde (12)
3
3
6
.37 (s, 1H, ArH), 7.43 (t, 1H, J = 8.0 Hz, ArH), 7.93 (d, 1H,
J = 6.8 Hz, ArH), 8.32 (brs, 1H, -OH), 8.59 (d, 1H, J = 8.4 Hz, To a solution of 2-Methyl-4-morpholin-4-yl-8-trifluorom-
ArH). LC/MS (ESI-MS) m/z = 228.2 (M+1)
ethyl-quinoline (11) (10 g, 0.033 mol.) in 1,4-dioxane (100
vol.) was added selenium dioxide (4.11 g, 0.037 mol.).
This was heated with stirring at 90 °C for 1 h. The reac-
tion was monitored by TLC analysis. The reaction mixture
was cooled to room temperature and filtered to remove
inorganics. The filtrate was dried over sodium sulphate,
Preparation of 4-Chloro-2-methyl-8-trifluoromethyl-
quinoline (10)
A solution of 2-Methyl-8-trifluoromethyl-quinoline-4-ol (9) filtered and concentrated under reduced pressure at
(
26 g, 0.114 mol.) in phosphoryl chloride (26 mL, 1 vol.) was 40-45 °C to yield the crude product as a brown solid. It
stirred at 80 °C for 2 h. The reaction was monitored by TLC was purified by flash chromatography using 60 % ethyl
analysis. When the reaction was complete, the reaction acetate in hexane. Yield: 6 g (57.3 %).
1
mixture was cooled to room temperature. The organic
H NMR (CDCl , 400 MHz) δ (ppm): 3.29 (t, 4H, -CH ),
3
2
layer was concentrated under high vacuum to remove 4.02 (t, 4H, -CH ), 7.57 (s, 1H, ArH), 7.67 (t, 1H, J = 8.0 Hz,
2
excess phosphoryl chloride. The resulting brown residue ArH), 8.12 (d, 1H, J = 4 Hz, ArH), 8.28 (d, 1H, J = 8 Hz), 10.18
was poured into ice-cold water and basified using 10 % (s, 1H, -CHO). LC/MS (ESI-MS) m/z = 311.6 (M+1)
sodium bicarbonate solution. The solid precipitated was
filtered, washed with water and dried to afford the desired
compound as a pale brown solid. Yield: 20 g (71.14 %)
General procedure for preparation of N-[1-{4-[4-(7-
1
H NMR (CDCl , 400 MHz) δ (ppm): 2.77 (s, 3H, -CH ), chloro-quinolin-4-yl)-piperazin-1-ylmethyl]-phenyl}-
3
3
7
.49 (s, 1H, ArH), 7.62 (t, 1H, J = 8.0 Hz, ArH), 8.10 (d, 1H, methylidene]-N’-aryl-hydrazine (QH-06 to QH-11)
J = 7.2 Hz, ArH), 8.40 (d, 1H, J = 8.4 Hz, ArH). LC/MS
ESI-MS) m/z = 246.5 (M+1) To a solution of 4-morpholin-4-yl-8-trifluoromethyl-
(
quinoline-2-carbaldehyde (11) (500 mg, 1.611 mmol.)
in ethanol (10 mL, 20 vol.) was added hydrazine
hydrochloride derivative (1.933 mol.). This was stirred at
ambient temperature for 5 h. The reaction was monitored
by TLC analysis. The reaction mixture was diluted with
Preparation of 2-Methyl-4-morpholin-4-yl-8-
trifluoromethyl-quinoline (11)
To a solution of 4-chloro-2-methyl-8-trifluoro-quinoline water and stirred for 30 min, and the solid precipitated
10) (20 g, 0.081 mol.) in isopropyl alcohol (100 mL) was was filtered to afford the desired compound.
(

ꢁ
Shruthi T G et al.: Design, Synthesis and Study of Antibacterial and Antitubercular Activity
1
42ꢁ
Preparation of N-[1-(4-morpholin-4-yl-8-trifluoromethyl-
quinolin-2-yl)-methylidene]-N’-phenyl-hydrazine
13C NMR (DMSO, 75 MHz) δ (ppm): 24.47, 25.38, 31.79,
32.49, 52.27, 58.70, 66.05, 104.23, 109.45, 121.62, 123.27,
123.87, 128.27, 128.72, 133.44, 143.94, 154.58, 156.70, 156.99.
LC/MS (ESI-MS) m/z = 407.7 (M+1)
(
QH-06)
This compound was prepared by reacting 4-morpholin-
-yl-8-trifluoromethyl-quinoline-2-carbaldehyde (500 mg,
4
1
.611 mmol.) with phenylhydrazine hydrochloride (279 mg, Preparation of N-(4-methoxy-phenyl)-N’-[1-(4-morpholin-
1.933 mmol.). Yield: 0.35 g (54.26 %)
4-yl-8-trifluoromethyl-quinolin-2-yl)-methylidene]-
1
H NMR (DMSO, 400 MHz) δ (ppm): 3.23 (t, 4H, -CH ), hydrazine (QH-09)
2
3
.91 (t, 4H, -CH ), 6.86 (t, 1H, J = 7.2 Hz, ArH), 7.18 (dd, 2H,
2
J = 8.4 2 Hz, ArH), 7.32-7.28 (m, 2H, ArH), 7.60 (t, 1H, J = 8 Hz, This compound was prepared by reacting 4-morpholin-
ArH), 7.64 (s, 1H, ArH), 7.98 (s, 1H, ArH), 8.08 (d, 1H, 4-yl-8-trifluoromethyl-quinoline-2-carbaldehyde (500 mg,
J = 6.8 Hz, ArH), 8.29 (d, 1H, J = 7.6 Hz), 10.93 (s, 1H, -NH). 1.611 mmol.) with 4-methoxyphenylhydrazine hydrochlo-
1
3
C NMR (DMSO, 100 MHz) δ (ppm): 52.21, 66.09, ride (337 mg, 1.933 mmol.). Yield: 0.4 g (57.7 %)
1
1
1
04.60,112.62, 120.04, 122.99, 123.82, 125.75, 126.13, 127.89,
HNMR(DMSO,400MHz)δ(ppm):3.22(t,4H,-CH )3.71
2
28.65, 129.26, 136.95, 144.24, 145.49, 156.02, 156.29. LC/MS (s,3H,-CH ),3.91(t,4H,-CH ),6.91(dd,2H,J=6.8,2Hz,ArH),
3
2
(
ESI-MS) m/z = 401.6 (M+1)
7.13 (dd, 2H, J = 6.8, 2 Hz, ArH), 7.58 (t, 1H, J = 7.6 Hz, ArH),
.62 (s, 1H, ArH), 7.91 (s, 1H), 8.07 (d, 1H, J = 7.6 Hz, ArH),
.28 (d, 1H, J = 8.4 Hz), 10.82 (s, 1H, -NH)
7
8
1
3
Preparation of N-(2,5-dimethyl-phenyl)-N’-[1-(4-
morpholin-4-yl-8-trifluoromethyl-quinolin-2-yl)-
methylidene]-hydrazine (QH-07)
C NMR (DMSO, 75 MHz) δ (ppm): 52.26, 55.30, 66.06,
104.36, 113.88, 114.21, 114.21, 114.84, 121.89, 122.31, 123.89,
125.93, 129.05, 129.59, 131.83, 137.74, 142.41, 154.04, 157.37.
LC/MS (ESI-MS) m/z = 430.43 (M+1)
This compound was prepared by reacting 4-morpholin-
-yl-8-trifluoromethyl-quinoline-2-carbaldehyde (500 mg,
4
1
.611 mmol.) with 2,5-dimethylphenylhydrazine hydro- Preparation of N-(4-fluoro-phenyl)-N’-[1-(4-morpholin-
chloride (333 mg, 1.933 mmol.). Yield: 0.36 g (52.17%)
4-yl-8-trifluoromethyl-quinolin-2-yl)-methylidene]-
1
H NMR (DMSO, 400 MHz) δ (ppm): 2.22 (s, 6H), 3.23 hydrazine (QH-10)
(
t, 4H, -CH ), 3.91 (t, 4H, -CH ), 6.92 (s, 1H, J = 7.2 Hz, ArH),
2
2
6
.99 (d, 1H, J = 8 Hz, ArH), 7.42 (d, 1H, J = 8 Hz, ArH), 7.60 (t, This compound was prepared by reacting 4-morpholin-
1
H, J = 8 Hz, ArH), 7.63 (s, 1H, ArH), 8.08 (d, 1H, ArH), 8.29 4-yl-8-trifluoromethyl-quinoline-2-carbaldehyde (500 mg,
d, 1H, J = 7.6 Hz), 8.30 (s, 1H), 10.08 (s, 1H, -NH). 1.611 mmol.) with 4-fluorophenylhydrazine hydrochloride
C NMR (DMSO, 100 MHz) δ (ppm): 23.71, 34.39, 51.98, (314 mg, 1.933 mmol.). Yield: 0.3 g (44.5 %)
(
1
3
1
5
1
1
2.99, 109.11, 121.65, 122.95, 124.34, 127.34, 127.89, 128.42,
H NMR (DMSO, 400 MHz) δ (ppm): 3.23 (t, 4H, -CH ),
2
34.69, 135.79, 138.43, 148.52, 148.98, 149.69, 151.52, 154.58, 3.91 (t, 4H, -CH ), 7.2-7.12 (m, 4H, ArH), 7.60 (t, 1H, ArH), 7.62
2
56.87, 167.62, 176.23. LC/MS (ESI-MS) m/z = 429.6 (M+1)
(s, 1H, ArH), 7.96 (s, 1H), 8.08 (d, 1H, J = 6.8 Hz, ArH), 8.29
d, 1H, J = 7.6 Hz), 10.93 (s, 1H, -NH).
(
1
3
C NMR (DMSO, 75 MHz) δ (ppm): 52.26, 66.13, 104.63,
Preparation of N-cyclohexyl-N’-[1-(4-morpholin-4-yl-8-
trifluoromethyl-quinolin-2-yl)-methylidene]-hydrazine
113.69, 115.98, 122.99, 123.87, 125.81, 127.86, 128.69, 136.94,
140.90, 145.49, 155.44, 155.98, 156.32, 157.78. LC/MS (ESI-
MS) m/z = 419.6 (M+1)
(
QH-08)
This compound was prepared by reacting 4-morpholin-
-yl-8-trifluoromethyl-quinoline-2-carbaldehyde (500 mg, Preparation of N-(4-isopropyl-phenyl)-N’-[1-(4-
.611 mmol.) with cyclohexylhydrazine hydrochloride morpholin-4-yl-8-trifluoromethyl-quinolin-2-yl)-
291 mg, 1.933 mmol.). Yield: 0.35 g (53.5 %) methylidene]-hydrazine (QH-11)
4
1
(
1
H NMR (DMSO, 400 MHz) δ (ppm): 1.32-1.35 (m, 5H),
.61-1.64 (m, 1H), 1.75-1.78 (m, 2H) 1.98-2.01 (m, 2H), 3.16 This compound was prepared by reacting 4-morpholin-
1
(
(
t, 4H, -CH ), 3.88 (t, 4H, -CH ), 7.01 (s, 1H, ArH), 7.10 4-yl-8-trifluoromethyl-quinoline-2-carbaldehyde (500 mg,
s, 1H, ArH), 7.61 (t, 1H, J = 7.6 Hz, ArH), 8.10 (d, 1H, J = 7.2 1.611 mmol.) with 4-isopropylphenylhydrazine hydrochlo-
ride (360 mg, 1.933 mmol.). Yield: 0.35 g (49 %)
2
2
Hz, ArH), 8.28 (d, 1H, J = 8 Hz), 12.01 (s, 1H, -NH).

Shruthi T G et al.: Design, Synthesis and Study of Antibacterial and Antitubercular Activityꢁ
ꢁ143
1
H NMR (DMSO, 400 MHz) δ (ppm): 1.19 (d, 6H, -CH ), to calculate the percentage cell growth. The % cell
3
2
.83 (sept, 1H, -CH), 3.23 (t, 4H, -CH ), 3.91 (t, 4H, -CH ), 7.11 growth values were plotted against the log of the tested
2
2
(
(
1
d, 2H, J = 8.4 Hz, ArH), 7.17 (d, 2H, J = 8.4 Hz, ArH), 7.59 concentration and analyzed using Graph Pad software to
t, 1H, J = 8 Hz, ArH), 7.63 (s, 1H), 7.94 (s, 1H, ArH), 8.08 (d, determine the IC value.
50
H, J = 6.8 Hz), 8.29 (d, 1H, J = 7.6 Hz, ArH), 10.85 (s, 1H, -NH).
13
C NMR (DMSO, 75 MHz) δ (ppm): 24.04, 32.69, 52.22,
6.10, 104.56, 112.69, 122.95, 122.50, 123.69, 125.89, 126.09,
6
1
Results and Discussion
Chemistry
26.97, 127.81, 128.60, 136.21, 140.14, 142.28, 145.52, 156.18.
LC/MS (ESI-MS) m/z = 443.7 (M+1)
Eleven new compounds containing a hybrid of substitu-
ted quinoline and hydrazone were synthesized according
to the synthetic methodologies presented in scheme 1
and scheme 2. In scheme 1, 3-chloro-phenylamine (1) was
converted into 2-[(3-chloro-phenylamino)-methylene]-
Biological Experiments
MIC Assay protocol (turbidometric)
The test compounds were dissolved in DMSO and double- malonic acid diethyl ester (2) by reaction with diethyl
diluted in a 10-concentration dose response (10-DR), and ethoxymethylenemalonate at 110 °C, and subsequent
5
the culture was added at an inoculum of 3-7X10 cfu/mL. cyclisation in Dowtherm medium at 240 °C afforded
The QC included media controls, growth controls and the 7-chloro-4-hydroxyquinoline (3). The chlorination of the
reference drug inhibitors (Rifampicin). The assay plates intermediate using POCl at reflux temperature resul-
3
were incubated at 37 °C for 15 days. The growth appeared ted in 4,7-dichloro-quinoline (4), and condensation of
as turbidity or as a deposit of cells at the bottom of the 4,7-dichloro-quinoline and piperazine in IPA at 95 °C
well. The results were enumerated and a turbidometric resulted in 7-chloro-4-piperazin-1-yl-quinoline (5) with
reading was noted. The first dilution that showed growth excellent yield. The common intermediate, 4-[4-(7-chloro-
inhibition was recorded as the MIC (Minimum Inhibitory quinolin-4-yl)-piperazin-1-ylmethyl]-benzaldehyde
Concentration).
(6), was synthesized by coupling of 4-chloromethyl-
benzaldehyde with 7-Chloro-4-piperazin-1-yl-quinoline.
The target compounds, namely quinoline derivatives
carrying the hydrazone moiety, viz. QH-01 to QH-05,
were synthesized by coupling 4-[4-(7-chloro-quino-
lin-4-yl)-piperazin-1-ylmethyl]-benzaldehyde (6) with
In Vitro Cytotoxicity Study of QH-02, QH-04, QH-05
&
QH-11
HepG2 cells grown in DMEM supplemented with 10 % fetal hydrazine hydrochloride molecules in ethanol with
bovine serum were trypsinized. The cells were counted, 96 good yield. In scheme 2, 2-trifluoromethyl aniline (8)
cell culture plates were filled with 12,000 HepG2 cells per was consequently converted into 2-methyl-8-trifluo-
well and the cells were allowed to grow for 48 hours in romethyl-quinolin-4-ol (9) via cyclisation using the
a CO incubator at 37 °C with 5 % CO . The 20 mM DMSO reagents ethyl acetoacetate and polyphosphoric acid
2
2
stocks of QH compounds and astemizole were used to at 150 °C. Intermediate (9) was refluxed with POCl to
3
prepare test solutions, and after 48 hours of plating the synthesis 4-chloro-2-methyl-8-trifluoro-quinoline (10).
HepG2 cells were treated with test/ control items ranging It was refluxed with morpholine using IPA solvent at
from 100-1.56 µM, in 0.2 mL of DMEM with 2 % FBS, and 90 °C to afford 2-methyl-4-morpholin-4-yl-8-trifluoro-
incubated for 24 hours in a CO incubator at 37 °C using methyl-quinoline (11). The key aldehyde intermediate,
2
5
% CO . About 50 µL of treatment medium was removed 4-morpholin-4-yl-8-trifluoromethyl-quinoline-2-carbal-
2
from each well of the plate and 50 µL of 1.4 mg/mL MTT dehyde (12), was prepared via oxidation using selenium
solution was added. The plates were then incubated for dioxide in 1,4-dioxane at 90 °C. The target compounds,
4
hours. After 4 hours, the medium was entirely removed namely quinoline molecules carrying hydrazone moiety,
from the wells and 0.2 mL of DMSO was added to solubilize viz. QH-06 to QH-11, were synthesized by coupling 4-mor-
the formazan crystals formed. The intensity of the color pholin-4-yl-8-trifluoromethyl-quinoline-2-carbaldehyde
was measured by reading the plate calorimetrically at 570 (12) with hydrazine hydrochloride molecules in ethanol.
nm. The blank subtracted OD values of the compound- All the newly synthesized compounds were characterized
1
13
treated wells were compared with vehicle-treated wells by H and C NMR and LC-MS studies.

ꢁ
1
44ꢁ
Shruthi T G et al.: Design, Synthesis and Study of Antibacterial and Antitubercular Activity
O
H
H
N
N
N
OH
N
Cl
N
N
Cl
NH
O
O
b
c
d
e
O
Cl
Cl
Cl
N
Cl
N
O
2
3
4
5
6
f
a
N
NH
Cl
NH2
1
R
N
1
N
N
Cl
QH-01 to QH-05
Intermediate 5C:
O
O
O
H
H
g
h
H
H
HO
Cl
O
5a
5b
5c
Scheme 1ꢂSynthetic route for quinoline hydrazone derivatives (QH-01 to QH-05).
O
N
OH
Cl
N
i
j
k
NH2
N
F
F
N
F
F
F
F
F
F
F
F
F
F
8
9
10
11
l
O
O
N
N
N
m
H
N
N
O
F
F
NHR
F
F
F
F
QH-06 to QH-11
12
Scheme 2ꢂSynthetic route of quinoline hydrazone derivatives (QH-06 to QH-11).
Reagents and conditions: (a) diethyl ethoxymethy- Biological Investigations
lenemalonate, 110 °C; (b) Dowtherm medium, 240 °C;
(
c) POCl , reflux; (d) piperazine, IPA, 95 °C; (e) Et N, Antituberculosis studies
3
3
ACN, DMF, RT; (f) hydrazine hydrochloride compounds,
ethanol, ambient temperature; (g) sodium borohydride, The antitubercular activity of compounds QH-01 to
THF, methanol, 0 °C; (h) SOCl , DMF, RT.
QH-11 was evaluated against Mtb WT H37Rv using the
2
Reagents and conditions: (i) ethyl acetoacetate, poly- broth microdilution method [27]. A turbidometric assay
phosphoric acid 150 °C; (j) POCl , reflux; (k) morpholine, was employed and the results were counted. Rifampicin
3
IPA, 90 °C; (l) selenium dioxide, 1,4-dioxane, 90 °C; (m) (RIF) was used as a standard drug and the first dilution
hydrazine hydrochloride molecules, RT.
that showed growth inhibition was recorded as the MIC

Shruthi T G et al.: Design, Synthesis and Study of Antibacterial and Antitubercular Activityꢁ
ꢁ145
(
Minimum Inhibitory Concentration). The MIC (µg/mL) of hydrazones containing 4-flouro phenyl, 4-tolyl and
values of all compounds against Mtb strain H37Rv are 4-isopropyl phenyl in QH-02, QH-04 and QH-05 respec-
tabulated in table 1. tively. The hydrazone and quinoline groups are bridged by
Antituberculosis screening data revealed that com- a piperazine ring in the compound QH-01 to QH-05. These
pounds QH-02, QH-04 and QH-05 possessed a mode- new molecules were found to be good starting points to
rately promising inhibitory activity of MIC 4 µg/mL. This find lead molecules to combat tuberculosis.
activity is attributed to the presence of the chloro group
at position 7 of the quinoline ring and the presence
Antimicrobial studies
Table 1ꢂAntitubercular activity of quinoline derivatives carrying
hydrazone against Mtb strain H37Rv.
All compounds (QH-01 to QH-11) were tested against
Gram Positive and Gram Negative pathogen strains such
Sl.No.
Compound ID
MIC_Mtb
(µg/mL)
Cytotoxicity IC
(µM)
as Escherichia coli (ATCC 25922), Pseudomonas aeruginosa
(ATCC 15442), Enterococcus faecium (ATCC 51559),
Staphylococcus aureus (ATCC 33591), Klebsiella pneumonia
(ATCC 700603) and Acinetobacter baumanii (ATCC 19606).
The assay plates were incubated for 24 hours at 37 °C. At
the end of the assay visual turbidometric readings were
taken and the results were noted. The MIC (µg/mL) values
of all compounds against bacterial strains are tabulated in
table 2. Vancomycin and Ciprofloxacin were used as a
standard. QH-02 showed promising activity of MIC 4 and
ꢀ
ꢁ
(
QH-XX)
QH-ꢄꢃ
QH-ꢄꢇ
QH-ꢄꢈ
QH-ꢄꢆ
QH-ꢄꢉ
QH-ꢄꢅ
QH-ꢄꢊ
QH-ꢄꢋ
QH-ꢄꢌ
QH-ꢃꢄ
QH-ꢃꢃ
RIF*
ꢃ
ꢅꢆ
ꢆ
-
ꢇ
>ꢃꢄꢄ
ꢈ
ꢃꢅ
ꢆ
-
ꢆ
>ꢃꢄꢄ
ꢉ
ꢆ
>ꢃꢄꢄ
ꢅ
ꢈꢇ
ꢈꢇ
ꢈꢇ
ꢈꢇ
ꢅꢆ
ꢃꢅ
ꢄ.ꢄꢇꢉ
-
ꢊ
-
ꢋ
-
2
µg/mL against Escherichia coli and Staphylococcus aureus
ꢌ
-
strains, respectively. QH-04, QH-05 and QH-11 showed
promisingactivityofMIC2µg/mLagainstEscherichiacoliand
MIC 4, 2 and 1 µg/mL against Acinetobacter baumaniistains
respectively. QH-04 and QH-11 showed promising activity of
MIC 2 µg/mL against Staphylococcus aureus.
ꢃꢄ
ꢃꢃ
ꢃꢇ
-
>ꢃꢄꢄ
-
*
Rifampicin (RIF) was used as a control against Mtb strain H37Rv
Table 2ꢂAntimicrobial activity of quinoline hydrazone derivatives against bacterial strains.
Compound
ID
MIC (µg/mL)
Escherichia
coli
ATCC ꢂꢀꢃꢂꢂ
Pseudomons
aeruginosa
ATCC ꢄꢀꢅꢅꢂ
Enterococcus
Staphylococcus
aureus
Klebsiella
pneumoniae
ATCC ꢇꢁꢁꢈꢁꢆ
Acinetobacter
baumanii
ATCC ꢄꢃꢈꢁꢈ
faecium
ATCC ꢀꢄꢀꢀꢃ
ATCC ꢆꢆꢀꢃꢄ
QH-ꢄꢃ
>ꢈꢇ
ꢅ
>ꢈꢇ
ꢂ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
>ꢃꢅ
ꢄ.ꢇꢉ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
ꢆ
>ꢈꢇ
ꢂ
>ꢈꢇ
ꢂ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
ꢂ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
ꢄ.ꢃꢇꢉ
>ꢃꢅ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
ꢅ
QH-ꢄꢇ
QH-ꢄꢈ
QH-ꢄꢆ
QH-ꢄꢉ
ꢂ
ꢂ
QH-ꢄꢅ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
ꢂ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
>ꢈꢇ
ꢄ
QH-ꢄꢊ
QH-ꢄꢋ
QH-ꢄꢌ
QH-ꢃꢄ
QH-ꢃꢃ
Vancomycin
Ciprofloxacin
>ꢃꢅ
ꢄ.ꢄꢈꢃꢇ
ꢄ.ꢉ
ꢃ
ꢄ.ꢉ
>ꢃꢅ
ꢄ.ꢉ

ꢁ
Shruthi T G et al.: Design, Synthesis and Study of Antibacterial and Antitubercular Activity
1
46ꢁ
Cytotoxicity studies of QH-02, QH-04, QH-05 and QH-11
References
[
1] World Health Organization. Global tuberculosis report 2018.
Geneva: World Health Organization; 2018.
2] Berry H, Coquelin JP, Gordon A, Seymour D. Antrafenine,
naproxen and placebo in osteoarthritis: a comparative study.
Br J Rheumatol. 1983;2(22):89–94.
We evaluated the cytotoxicity of QH-02, QH-04, QH-05
and QH-11 against the HepG2 cell line by MTT Cytotoxicity
assay [28]. After 48 hours of plating, HepG2 cells were
treated with test/ control compounds in concentrations
[
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5
0
and QH-11 were found to be > 100 µM (IC values are
5
0
tabulated in Table 1). Astemizole was used as a control and
the IC value of astemizole was found to be 7.95 µM. These
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Conflicts of Interest: The authors state no conflict of
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