Antibacterial and anticancer properties of new fluoroquinolones

Article abstract of DOI:10.14233/ajchem.2020.22413

Fluoroquinolones are clinically successful antibacterial agents. In this work a series of novel 7-substituted anilino-8-nitrofluoroquinolone esters (3-9), acids (10-16) and 8-amino reduced derivatives (17-23) of the later compounds were successfully prepa

Full text of DOI:10.14233/ajchem.2020.22413

Asian Journal of Chemistry; Vol. 32, No. 2 (2020), 427-434
A
SIAN
J
OURNAL OF HEMISTRY
C
https://doi.org/10.14233/ajchem.2020.22413
Antibacterial and Anticancer Properties of New Fluoroquinolones
1,*,
2,
3,
2,
MAHA R. AL RIMAWI
, YUSUF M. AL-HIARI , AMAL G. AL-BAKRI and SANAA K. BARDAWEEL
1Department of Allied and Medical Sciences, Zarqa University College, Al-Balqa Applied University, Zarqa-313, Jordan
2Department of Pharmaceutical Sciences, School of Pharmacy, The University of Jordan, Amman-11942, Jordan
3Department of Pharmaceutics and Pharmaceutical Technology, School of Pharmacy, The University of Jordan, Amman-11942, Jordan.
*Corresponding author: E-mail: mah_rmw@bau.edu.jo
Received: 25 August 2019;
Accepted: 31 October 2019;
Published online: 30 December 2019;
AJC-19738
Fluoroquinolones are clinically successful antibacterial agents. In this work a series of novel 7-substituted anilino-8-nitrofluoroquinolone
esters (3-9), acids (10-16) and 8-amino reduced derivatives (17-23) of the later compounds were successfully prepared and characterized
using spectroscopic techniques. All the compounds tested (10-23) showed good antibacterial activity against both Gram-positive and
Gram- negative standard bacterial strains. Interestingly, 8-amino reduced derivatives (17-22) were more active against both standard
strains than their 8-nitro acid analogues (10-15). Moreover, some targeted compounds have shown reasonable activity mainly against
resistant gram positive bacteria. In particular compounds 10, 12 and 16 displayed a potent activity against methicillin resistant S. aureus
(MRSA) with MIC values of 4.7, 2.3 and 1.2 µg/mL, respectively. Lipophilicity could be a plausible explanation of such higher activity
against the gram positive resistant strain (MRSA). Biological screening of cytotoxic activity against five cancer cell lines using an in vitro
cell culture system was achieved for all tested compounds. These derivatives have shown weak activity for most of them. Interestingly,
more lipophilic nitroacids (10-15) were more active than their analogous reduced acids (17-22).
Keywords: Fluoroquinolones, Antibacterial activity, Anticancer activity, Cell lines, MRSA.
and mortality throughout the world and therefore there is consi-
derable recent interest in developing new anticancer agent with
new mode of action to overcome increased resistance against
current anticancer drugs [10]. Fluoroquinolones were recently
introduced as anticancer agents with new mode of action that
will overwhelmed resistance and side effects of available thera-
pies including chemotherapy, surgery and radiotherapy [9].
Vasoroxin (voreloxin) is an anticancer quinolone that inhi-
bits topoisomerase-II leading to cell cycle arrest and apoptosis
[11].Vasoroxin has currently completed phase III clinical trial
for acute myelocytic leukemia (AML) [12]. Owing to the pote-
ntial biological interest of these fluoroquinolones including
anticancer and antibacterial activity and to overcome the problem
of resistance, a new series of lipophilic fluoroquinolones were
designed to exhibit substituted anilines on C-7; mainly methyl
and methoxy aniline derivatives. All these derivatives will be
screened for their antibacterial activity against standard and
resistant gram positive and negative strains. Due to availability
of cancer cell lines and potential anticancer activity of anti-
INTRODUCTION
Many antibacterial agents have been introduced into clinical
use with a significant improvement in their antibacterial spectrum
and activity [1,2]. Fluoroquinolone antibacterial agents, such
as ciprofloxacin and norfloxacin are among the most successful
clinically active drugs in the anti-infective chemotherapy field
and constitute a major class of broad spectrum antibacterial
agents against both Gram-positive and Gram-negative strains
[3,4]. However, the extensive and naive misuse of these drugs
led to the emergence of bacterial resistance against these agents
[5-7].
Although antibacterial quinolones are known as potent
inhibitors of bacterial DNA gyrase and topoisomerase IV needed
for DNA replication and transcription, new quinolone deriva-
tives have inhibitory effect against eukaryote topoisomerase
II leading to cytotoxic activity against some cancerous cells
[8,9]. Despite great advances in modes of treatment in cancer
therapy, cancer remains a major leading cause of morbidity
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428 Al Rimawi et al.
Asian J. Chem.
bacterial fluoroquinolones, new acid (10-15) and reduced (17-
22) derivatives will be screened for their anticancer activity
against five cancer cell lines (T47D, MCF-7, A498, HeLa and
PC-3).
This work involves the preparation and characterization
of a series of novel 7-substituted anilino-8-nitrofluoroquinolone
esters (ethyl 7-substituted anilino-1-cyclopropyl-6-fluoro-8-
nitro-4-oxo-1,4-dihydroquinoline-3-carboxylate (3-9), their
hydrolyzed acids (7-substituted anilino-1-cyclopropyl-6-fluoro-
8-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid) (10-16);
and their reduced 8-amino derivatives (8-amino-7-substituted
anilino-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-
3-carboxylic acid) (17-23).
7-Aniline derivatives (3, 10 and 17), 2-methyl phenyl
derivatives (6, 13 and 20), 3-methoxy phenyl derivatives (8,
15 and 22) and 2-methoxyphenyl derivatives (9, 16 and 23)
were synthesized for the first time and their experimental data
are within the experimental data. Whereas, 4-methyl aniline
derivatives (4, 11 and 18), 3-methyl aniline derivatives (5, 12
and 19) and 4-methoxy aniline (7, 14 and 21) were previously
reported by our group [13,14]. Synthesis of cipro ester (2)
has been reported in the literature and was followed in this work
with minor modifications [13,15].
A simple, optimized and efficient pathway was used to
synthesize substituted aniline derivatives in which aniline deri-
vatives were introduced starting from synthone 2 (ester path-
way) using DMSO as a solvent and few drops of pyridine under
reflux and anhydrous conditions. The ester pathway furnished
7-anilino esters (3-9) with high yield and good purity for most
compounds. Crystallization was enough to get pure crystalline
solids of target esters and simple dispersion from hexane or
petroleum ether produced pure products of most esters without
the need for purification or chromatographic separation (3-9).
The esters (3-9) were hydrolyzed successfully in ethanol
and 12 N HCl (3:7), under reflux at 80-90 ºC for 24-48 h;
providing high yield upon precipitation. Then the resulting
acid derivatives (10-16) were further reduced using aqueous
SnCl2/HCl at room temperature to get 8-amino acid analogues
(17-23). All intermediates and targets were successfully
purified and characterized by NMR, MS and IR. Screening
of the biological activity of obtained pure acid and reduced
fluoroquinolone acid derivatives against both standard and
resistant strains of bacteria and five human cancer cell lines
was then carried out. The intermediates 3-9 were not tested due
to negligible activity in their ester form.
and suspension were prepared as described by the manufacturer
and autoclaved (Raypa Steam Sterilizer, Spain) at 121 ºC for
15 min. Universal Microplate Reader, ELx 800UV, Biotech
Instruments (USA) were used. Staphylococcus aureus ATCC
6538P, Escherichia coli ATCC 8739 and methicillin resistant
Staphylococcus aureusATCC 43300 (MRSA), Acinetobacter
baumannii F24 (environmental strain) and clinical Resistant
Escherichia coli strains (1122, 1058 & 990) were receieved as
a kind gift from Prof. Asem Shehabi, Faculty of Medicine,
University of Jordan. Ciprofloxacin hydrochloride was gifted
from Al-Hikma Pharmaceutical company.
NMR were recorded on Bruker,Avance DPX-300 spectro-
meter and Bruker Avance 500 MHz Ultrashield spectrometer
at The University of Jordan. Chemical shifts are reported in
ppm related to tetramethylsilane (TMS) as the internal standard
using DMSO-d6 and CDCl3. Infrared (IR) spectra were recorded
using Shimadzu 8400F FT-IR spectrophotometer. Samples
were prepared as KBr (Merck, Dermstadt, Germany) discs.
Melting points were determined in open capillaries on a
Stuart scientific electro-thermal melting point apparatus, and
are uncorrected. High resolution mass spectra (HRMS) were
measured in positive ion mode using electrospray ionization
(ESI) technique by collision-induced dissociation on a Bruker
APEX-4 (7 Tesla) instrument at The University of Jordan. The
samples were dissolved in acetonitrile, diluted in spray solution
(methanol/water 1:1 v/v + 0.1 formic acid) and infused using
a syringe pump with a flow rate of 2 µL/min. External calibra-
tion was conducted using arginine cluster in a mass range m/z
175-871.
Thin layer chromatography (TLC) was performed on alumi-
num plates pre-coated with fluorescent silica gel GF254 from
ALBET (Germany) and were visualized under UV lamp, Spectro-
line cabinet, Model CX-20 (USA).
Mobile phase mixtures were as follows: system 1: CHCl3:
MeOH: FA) (94: 5: 1); system 2: CHCl3:MeOH:FA (90:10:1),
system 3: Hexane:ethyl acetate (50:50) and; system 4: system
1:system 3 (50: 50).
7-Chloro-1-cyclopropyl-6-fluoro-8-nitro-4-oxo-1,4-
dihydroquinoline-3-carboxylate ester (2) was synthesized accor-
ding to the reported method (Scheme-I) [13,14].
General procedure for ester pathway to synthesized
compounds (3, 6, 8 and 9): Initially, 2 M equivalents of substi-
tuted aniline derivatives 1 were added into a solution containing
ethyl-7-chloro-1-cyclopropyl-6-fluoro-8-nitro-4-oxo-1,4-
dihydroquinoline-3-carboxylate (2) (1 g, 2.83 mmol) and 10-
15 mL of DMSO as a solvent and few drops of pyridine. The
mixture was refluxed for 65-70 ºC under anhydrous conditions.
Additional (0.5 molar equivalent) of aniline derivative was
added according to theTLC. The reaction mixture was monitored
until no starting material remained. The reaction was completed
within 2-7 days. Then, cooled mixture was left to crystallize
at room temperature and the product was filtered and left to
dry in a dark place. In this work, compounds 3, 6, 8 and 9 are
reported for the first time, whereas compounds 4, 5 and 7 were
synthesized according to the reported method [13].
EXPERIMENTAL
All chemicals, reagents and solvents were of analytical
grade and used without further purification. The starting mate-
rials involved in this work are: aniline, o-anisidine, o-toluidine
from Merck, (Darmstadt, Germany); m-anisidine and m-tolu-
dine fromAldrich Chemicals (England); p-toluidine, p-anisidine
from Fluka (Switzerland). Reducing agents used are stannous
chloride dihydrate crystals from Fluka (Switzerland), sodium
dithionate from Loba Chemie (India).
Ethyl 7-anilino-1-cyclopropyl-6-fluoro-8-nitro-4-oxo-
1,4-dihydroquinoline-3-carboxylate (3): Dark orange, yield:
51.7 % (0.6 g); m.p. 210-212 ºC (decomp.); Rf value in system
Nutrient broth, Mueller-Hinton broth and 0.5 McFarland
suspension were obtained from Oxoid (England); agar, broth

Vol. 32, No. 2 (2020)
Antibacterial and Anticancer Properties of New Fluoroquinolones 429
O
N
NH2
O
F
CO2Et
R1
R3
F
CO2Et
+
DMSO, pyridine
Reflux 70oC
Cl
R2
R2
N
H
N
NO2
R3
R1
NO2
1
2
3-9
O
N
O
5"
5
4
R3
F
COOH
R3
F
COOH
4"
6
4a
8a
6"
3
2
HCl/ EtOH
Reflux 80-85oC
SnCl2/ HCl
RT
7
3"
1"
R2
N
H
R2
N
N
8
H
1
2"
R1
NO2
R1
NH2
10-16
17-23
Compounds
7-Derivative
R1
R2
R3
C3
C3
Aniline
H
H
H
CH3
H
H
H
H
CH3
H
H
OCH3
H
H
CH3
H
H
OCH3
H
3,10,17
4,11,18
5,12,19
6,13,20
7,14,21
8,15,22
9,16,23
p-Toluidine
m-Toluidine
o-Toluidine
p-Anisidine
m-Anisidine
o-Anisidine
OCH3
H
Scheme-I: Synthesis of fluoroquinolone targets (3-23)
4 = 0.71. IR (KBr, νmax, cm-1): 3400, 3367, 1735, 1620, 1512,
1450, 1319, 1234. 1H NMR (300 MHz, CDCl3): δ 0.93, 1.14
(2m, 4H, H2-2′/H2-3′), 1.42 (t, J = 7.1 Hz, OCH2CH3), 3.65
(m, 1H, H-1′), 4.42 (q, J = 7.1 Hz, 2H, OCH2CH3), 7.03 (d, J
= 7.5 Hz, 2H, H-2′′/H-6′′), 7.17 (d,d, J = 7.4, 7.4 Hz, 1H, H-
4′′), 7.34 (d, d, J = 7.7, 7.8 Hz, 2H, H-3′′/H-5′′), 7.85 (br s,
1H, NH, exch.), 8.25 (d, 3JH-F = 12.0 Hz, 1H, H-5), 8.63 (s, 1H,
H-2). 13C NMR (75 MHz, CDCl3): δ 10.16 (C-2′/C-3′), 14.4
(CH3CH2), 38.78 (C-1′), 61.33 (CH2CH3), 112.88 (C-3), 117.1
(d, 2JC-F = 21.2 Hz, C-5), 118.28 (Ar-C), 122.59 (Ar-C), 124.78,
131.14, 133.23, 129.49 (Ar-C), 131.8 (d, 2JC-F = 14.4 Hz, C-7),
143.17 (N-CAr), 150.9 (d, 1JC-F = 254 Hz, C-6), 151.23 (C-2),
164.54 (CO2Et), 171.19 (C-4). HRMS (ESI, +ve): calculated
for C21H18N3O5FNa [M+Na]+: 434.11282. Found: 434.11227
Ethyl-1-cyclopropyl-6-fluoro-7-[(2-methyl phenyl)-
amino]-8-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylate
(6): Orange, yield: 38% (0.45 g); m.p.: 242-244 ºC (decomp.);
Rf value in system 1 = 0.75. IR (KBr, νmax, cm-1): 3459, 3355,
3071, 2924, 2931, 1727, 1620, 1527, 1464, 1337, 1310, 1232,
133.35 (d, 2JC-F = 15.4 Hz, C-7), 135.23 (C-8), 141.54 (C-1′′),
151.25 (C-2), 152.53 (d, 1JC-F = 253 Hz, C-6), 165.45 (C(3)-
CO2Et), 176.78 (C-4). HRMS: calculated for C22H20N3O5F [M]+:
425.13870. Found C22H21N3O5F [M+1]+: 426.14598.
Ethyl-1-cyclopropyl-6-fluoro-7-[(3-methoxy phenyl)-
amino]-8-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylate
(8): Orange, yield: 43% (0.80 g); m.p.: 234-237 ºC (decomp.);
Rf value in system 4 = 0.71. IR (KBr, νmax, cm-1): 3363, 2978,
1
2931, 1728, 1604, 1512, 1465, 1165, 1087, 1033. H NMR
(300 MHz, CDCl3): δ 1.04 (m, 4H, H2-2′/H2-3′), 1.29 (t, J =
7.4 Hz, 3H, OCH2CH3), 3.65 (m, 1H, H-1′), 3.75 (s, 3H, OCH3),
4.32 (q, J = 7.5 Hz, 2H, OCH2CH3), 6.57-6.62 (m, J = 8.5, 7.5
Hz, 3H, Ar-H), 7.76 (d,d, J = 4.0, Hz, 1H, Ar-H), 8.22 (d, JH-
F = 11.4 Hz, 1H, H-5), 8.84 (s, 1H, H-2), 8.96 (br s, 1H, NH,
exch.). 13C NMR (75 MHz, CDCl3): δ 10.14 (C-2′/C-3′), 14.33
(OCH2CH3), 38.70 (C-1′), 55.33 (OCH3), 61.19 (OCH2-CH3),
106.17 (C-3), 112.42 (d, JC-F = 3 Hz, C-4a), 112.91, 116.79 (d,
2JC-F = 21.0 Hz, C-5), 122.34, 127.82, 129.79, 131.20, 132.99,
133.38, 133.86, 150.91 (1JC-F = 250 Hz, C-6), 151.15 (C-2),
158.25 (C- 3′′), 164.59 (CO2Et), 172.52 (C-4). HRMS (ESI,
+ve): calculated for C22H20N3O6FNa [M+Na]+: 464.12338.
Found: 464.12283.
Ethyl-1-cyclopropyl-6-fluoro-7-[(2-methoxyphenyl)-
amino]-8-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylate
(9): Dark orange, yield: 24.1 % (0.45 g); m.p.: 200-205 ºC
(decomp.); Rf value in system 4 = 0.71. IR (KBr, νmax, cm-1):
3379, 2924, 2931, 1620, 1527, 1465, 1327, 1242, 1172, 1035.
1H NMR (300 MHz, CDCl3): δ 1.02 (m, 4H, H2-2′/H2-3′), 1.32
1
1153, 1045. H NMR (300 MHz, CDCl3): δ 1.12, 1.21 (2m,
4H, H2-2′/H2-3′), 1.42 (t, J = 7.4 Hz, 3H, OCH2CH3), 2.25 (s,
3H, CH3), 3.68 (m,1H, H-1′), 4.20 (q, J = 7.8 Hz, 2H,
OCH2CH3), 6.89-7.51 (m, 4H, Ar-H), 8.48 (d, 3JH-F = 13 Hz,
1H, H-5), 8.72 (br s, 1H, NH, exch.), 8.85 (s, 1H, H-2). 13C NMR
(75 MHz, DMSO-d6): δ 10.31 (C-2′/C-3′), 14.35 (OCH2CH3),
21.22 (Ar-CH3), 39.21 (C-1′), 55.56 (OCH2CH3), 110.42 (C-3),
2
115.57 (d, JC-F = 21.83 Hz, C-5), 118.12, 120.0, 121.36 (d,
3JC-F = 7.9 Hz, C-4a), 127.33, 129.7,131.24, 134.52 (C-8a),

430 Al Rimawi et al.
Asian J. Chem.
(t, J = 7.4 Hz, 3H, OCH2CH3), 3.60 (m,1H, H-1′), 3.77 (s, 3H,
OCH3), 4.28 (q, J = 7.6 Hz, 2H, OCH2CH3), 7.0-7.41 (m, 4H,
Ar-H), 7.98 (d, 3JH-F = 12 Hz, 1H, H-5), 8.78 (br s, 1H, NH,
exch.), 8.79 (s, 1H, H-2). 13C NMR (75 MHz, CDCl3): δ 10.10
(C-2′/C-3′), 14.52 (OCH2CH3), 39.82 (C-1′), 55.33 (OCH3),
61.95 (OCH2CH3), 102.21 (d, 2JC-F = 20.10 Hz, C-5), 107.25
1-Cyclopropyl-6-fluoro-7-[(3-methoxyphenyl)amino]-
8-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (15):
Dark yellow to faint brown. Yield: 78 % (0.28 g); m.p. 245-
247 ºC (decomp.); Rf value in system 4 = 0.65. IR (KBr, νmax
,
cm-1): 3448, 3363, 3063, 2924, 2854, 2360, 1728, 1612, 1512,
1
1319, 1280, 1157, 1049. H NMR (300 MHz, DMSO-d6): δ
(C-3), 108.92, 112.72, 116.21, 121.29,126.15, 127.45, 127.61,
1.06 (m, 4H, H2-2′/H2-3′), 3.71 (s, 3H, OCH3), 3.78 (m, 1H, H-
1′), 6.55-6.44 (m, J = 8.6, 7.6 Hz, 3H, Ar-H), 7.76 (d, d, J =
8.1, 7.9 Hz, 1H, Ar-H), 8.22 (d, JH-F = 11.5 Hz, 1H, H-5), 8.84
(s, 1H, H-2), 8.96 (br s, 1H, NH, exch.), 13.25 (s, 1H, COOH).
13C NMR (75 MHz, DMSO-d6): δ 10.58 (C-2′/C-3′), 40.92 (C
-1′), 55.52 (OCH3), 105.01 (Ar-C), 108.80 (Ar-C), 109.39 (C-3),
111.32 (Ar-C), 114.82 (d, d, 2JC-F = 21.3 Hz, C-5), 121.77 (d,
3JC-F = 7.2 Hz, C-4a), 130.03 (Ar-C), 132.66 (d, 1JC-F = 16 Hz,
C-7), 133.81 (C-8a), 135.41 (C-8), 143.56 (C-1′′), 152.56 (C-2),
153.32 (d, 1JC-F = 253 Hz, C-6), 160.25 (C-3′′), 165.25 (COOH),
175.89 (d, 4JC-F = 2.5 Hz, C-4). HRMS (ESI +ve): EA calculated
for C20H16N3O6FNa [M+Na ]+: 436.09208. Found: 436.09153.
1-Cyclopropyl-6-fluoro-7-[(2-methoxyphenyl)amino]-
8-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (16):
Dark brown, yield: 51.78 % (0.145 g); m.p. 239-244 ºC
(decomp.); Rf value in system 4 = 0.65. IR (KBr, νmax, cm-1):
3410, 3078, 3016, 2926, 2839, 2492, 1728, 1627, 1519, 1465,
1311, 1249, 1095, 1026. 1H NMR (500 MHz, DMSO-d6): 1.04
(2m, 4H, H2-2′/H2-3′), 3.71 (s, 1H, OCH3), 3.76 (m, 1H, H-1′),
6.92 (d, d, J = 7.55, 7.55 Hz, 1H, H-4′′), 7.04 (d, J = 8.05 Hz,
1H, H-3′′), 7.15 (m, 2H, H-5′′ & 6′′), 8.10 (d, JH-F = 12.1 Hz,
1H, H-5), 8.61 (br s, 1H, NH, exch.), 8.83 (s, 1H, H-2, 14.54
(s, 1H, COOH). 13C NMR (125 MHz, DMSO-d6): δ 10.42 (C-
2′/C-3′), 40.44 (C-1′), 56.14 (OCH3), 113.81 (d, 2JC-F = 21.54
Hz, C-5), 109.46 (C-3), 111.97 (Ar-CH), 119.59 (d, J = 7.03
Hz, C-4a), 120.84 (Ar-CH), 122.77 (Ar-CH), 125.89 (Ar-CH),
129.45 (C-8), 132.17 (C-8a), 134.34 (C-1′′), 134.86 (d, J =
14.6 Hz, C-7), 152.06 (C-2′′), 152.15 (d, 1JC-F = 252.46 Hz, C-6),
152.36 (C-2), 165.29 (COOH), 175.74 (C-4). HRMS (ESI +ve):
EA calculated for C20H16N3O6NaF [M+Na]+: 436.09208. Found:
436.09211.
Preparation of Compounds (17, 20, 22 and 23) by reduc-
tion of compounds (10, 13, 15 and 16): In this work, comp-
ounds 17, 20, 22 and 23 are reported for the first time, whereas
compounds 18, 19 and 21 were previously reported [13,14]
and re-synthesized in this work for biological screening.
Main procedure: Stannous chloride/HCl method (major):
A mixture of the resulting acid derivatives (10, 13, 15 and 16)
in a 5-10 mL of 12 N HCl was left stirring in an ice-bath (2-5
ºC) for 15 min.After that an ice bath was removed, excess SnCl2
was added portion-wise, and the reaction mixture was left stir-
ring overnight and monitored by TLC until completion. Then,
the reaction mixture was poured onto a crushed ice to precipi-
tate the product which was collected by filtration and dried.
This reduction method was successful in reducing most of the
target models with good yield.
1
140.22 (C-1′′), 140.89 (C-8), 151.23 (C-2), 151.59 (d, JC-F
=
254 Hz, C-6), 154.62 (C-2′′), 167.92 (CO2Et), 175.98 (C-4).
HRMS (ESI, +ve): EA calculated for C22H20 N3O6FNa [M+
Na]+: 464.12338. Found: 464.12278.
Synthesis of compounds (10, 13, 15 and 16) by hydro-
lysis of compounds (3, 6, 8 and 9): In this work, compounds
10, 13, 15 and 16 are reported for the first time, whereas comp-
ounds 11, 12 and 14 were previously reported [13] and resynthe-
sized for biological screening
General procedure: The resulting compounds, ethyl-7-
(substituted anilino)-1-cyclopropyl-6-fluoro-8-nitro-4-oxo-
1,4-dihydroquinoline-3-carboxylate (3, 6, 8, 9) were dissolved
in a mixture of absolute ethanol and 12 N HCl (3:7), under
reflux at 80-90 ºC for 24-48 h. The reaction was monitored by
TLC. At the end of reaction, the reaction mixture was poured
onto a crushed ice and the pure precipitate was collected by
filtration and dried at room temperature.
7-Anilino-1-cyclopropyl-6-fluoro-8-nitro-4-oxo-1,4-
dihydroquinoline-3-carboxylic acid (10): Bright orange,
yield: 76.1 % (0.245 g); m.p. 210-214 ºC (decomp.); Rf value
in system 4 = 0.55. IR (KBr, νmax, cm-1): 3448, 3363, 3055,
1
2399, 1735, 1620, 1512, 1450, 1319, 1234, 1026. H NMR
(300 MHz, DMSO-d6): δ 1.07 (2m, 4H, H2-2′/H2-3′), 3.75 (m,
1H, H-1′), 7.05 (m, 2H, Ar-H ), 7.27 (d, d, J = 7.4, 7.5 Hz, 2H,
Ar-H), 7.43 (d, J = 4.2 Hz, 1H, Ar-H), 8.20 (d, 3JH-F = 11.6 Hz,
1H, H-5), 8.85 (s, 1H, H-2), 9.05 (br s, 1H, NH, exch.), 14.52
(br s, 1H, COOH). 13C NMR (75 MHz, DMSO-d6): δ 10.57
(C-2′/C-3′), 39.65 (C-1′), 110.4 (d, 1JC-F = 21.5 Hz, C-5), 119.3,
121.27, 121.88,122.23, 124.41, 126.19, 126.65, 129.9, 132.97,
133.129, 148.25, 151.9 (C-2), 152.52 (d, JC-F = 253 Hz, C-6),
165.26 (COOH), 175.84 (C-4). HRMS (ESI, +ve): EA
calculated for C19H14N3O5FNa [M+Na]+: 406.08152. Found:
406.08097.
1-Cyclopropyl-6-fluoro-7-[(2-methylphenyl)amino]-8-
nitro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (13):
Faint orange, yield: 67 % (0.28 g); m.p. 234-236 ºC (decomp.);
Rf value in system 4: 0.62. IR (KBr, νmax, cm-1): 3465-3374 br,
3092, 2935, 2923, 1735, 1645, 1552, 1477, 1345, 1301, 1222,
1
1095, 1025. H NMR (500 MHz, CDCl3): δ 1.02, 1.03 (2m,
4H, H2-2′/H2-3′), 2.25 (s, 3H, CH3), 3.74 (m, 1H, H-1′), 7.02
(d, J = 7.65Hz, Ar-H), 7.13 (m, 2H, Ar-H), 7.25 (dd, J = 7.4,
5.5 Hz, Ar-H), 8.10 (d, 3JH-F = 11.9 Hz, 1H, H-5), 8.59 (br s,
1H, NH, exch.), 8.83 (s, 1H, H-2), 14.53 (brs, 1H, COOH).
13C NMR (125 MHz, DMSO-d6): δ 10.54 (C-2′/C-3′), 18.25
(Ar-CH3), 40.36 (C-1 ), 109.29 (C-3), 114.13 (d, 2JC-F = 21.21
Hz, C-5), 119.15 (d, J=6.8Hz, C-8a), 123.95 (CH-Ar), 126.07
(CH-Ar), 126.76 (CH-Ar), 130.92 (CH-Ar), 131.59 (C-4a),
132.56 (C-2′′), 134.38 (C-8), 135.58 (d, 2JC-F = 14.2 Hz, C-7),
139.63 (C-1′′), 151.72 (d, 1JC-F = 251.46 Hz, C-6), 152.36 (C-
2), 165.29 (C(3)-CO2H), 175.72 (C-4). HRMS: calculated for
C20H17N3O5F [M+1]+: 398.11523. Found: 398.11535.
Sodium dithionate/K2CO3 method: To a stirred solution
of resulting acid derivatives (10, 13, 15 and 16), potassium
carbonate in 5 mL water; an aqueous solution of sodium
dithionite (2 mmol) in 5 mL water was added dropwise. The
reaction mixture left stirring at room temperature overnight
and monitored by TLC.At the end of reaction, pH of the solution

Vol. 32, No. 2 (2020)
Antibacterial and Anticancer Properties of New Fluoroquinolones 431
was adjusted to about 4 by gradual addition of 3 N HCl. The
precipitate product was filtered, washed with water and left to
dry. This reduction method produced the compounds in low
yield and with some side products that needed chromatographic
separation.
8-Amino-1-cyclopropyl-6-fluoro-7-[(2-methoxyphenyl)-
amino]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (23):
Dark greenish, yield: 95 % (0.145 g); m.p. 187-192 ºC (decomp.);
Rf value in system 4 = 0.26. IR (KBr, νmax, cm-1): 3475-3324,
3084, 2925, 2347, 1610, 1522, 1462, 1275, 1167, 1087, 1055.
1H NMR (300 MHz, DMSO-d6): δ 1.17, 1.23 (2m, 4H, H2-2′/
H2-3′), 3.89 (s, 1H, OCH3), 4.54 (br s, 1H, H-1′), 5.80 (br s,
2H, NH2), 6.29 (d, J = 7.25 Hz, 1H, H-3′′), 6.76 (m, J = 8.3 Hz,
2H, H-4′′/H-5′′), 6.94 (br s, 1H, NH, exch.), 6.98 (d, J = 7.5 Hz,
1H, H-6′′), 7.34 (d, 3JH-F = 9.6 Hz, 1H, H-5), 8.76 (s, 1H, H-2),
15.07 (s, 1H, COOH). 13C NMR (125 MHz, DMSO-d6): δ10.73
(C-2′/C-3′), 40.35 (C-1′), 56.15 (OCH3), 98.31 (d, 2JC-F = 23.4
Hz, C-5), 106.62 (C-3), 111.37 (Ar-CH), 112.74 (Ar-CH),
8-Amino-7-anilino-1-cyclopropyl-6-fluoro-4-oxo-1,4-
dihydroquinoline-3-carboxylic acid (17): Dark yellow, yield:
73.06 % (0.08 g); m.p. 175-180 ºC (decomp.); Rf value in
system 4 = 0.25. IR (KBr, νmax, cm-1): 3450, 3006, 2893, 2816,
1720, 1604, 1504, 1450, 1334, 1180, 1087. 1H NMR (300 MHz,
DMSO-d6): δ 1.20 (2m, 4H, H2-2′/H2-3′), 4.53 (m,1H, H-1′),
5.75 (br s, 2H, NH2), 6.68 (m, 2H, Ar-H), 7.16 (m, 2H, Ar-H),
7.37 (m, 1H, Ar-H), 7.81 (br d, 1H, H-5), 8.76 (s, 1H, H-2),
9.10 (br s, 1H, NH, exch.), 15.12 (br s, 1H, COOH). 13C NMR
(75 MHz, DMSO-d6): δ 10.63 (C-2′/C-3′), 40.93 (C-1′), 97.76
(C-3), 98.15 (d, 2JC-F = 23 Hz, C-5), 106.66, 114.6 (C-2′′/C- 6′′),
119.23 (C- 4′′), 120.75, 125.28, 127.73, 129.34 (C-3′′/C-5′′),
139.40, 145.02 (C-1′′), 151.1 (C-2), 152.3 (d, 1JC-F = 251 Hz,
C-6), 166.27 (COOH), 177.32 (C-4). HRMS (ESI, +ve): EA
calculated for C19H17N3O3F [M+H]+: 354.1254. Found: 354.1249.
8-Amino-1-cyclopropyl-6-fluoro-7-[(2-methylphenyl)-
amino]-8-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylic
acid (20): Faint yellow, yield: 68 % (0.31 g); m.p. 190-195 ºC
(decomp.); Rf value in system 4 = 0.31. IR (KBr, νmax, cm-1):
3460-3343, 3085, 2922, 2905, 1745, 1655, 1556, 1480, 1375,
2
119.48 (Ar-CH), 120.95 (d, JC-F = 17.13 Hz, C-7), 121.16
(Ar-CH), 125.52 (d, J = 9.6 Hz, C-4a), 127.65 (C-8a), 134.28
(C-8), 139.88 (d, J = 3.95 Hz, C-1′′), 148.10 (C-2′′), 151.07 (C-
2), 157.21 (d, 1JC-F = 243.58 Hz, C-6), 166.28 (COOH), 177.32
(C-4). HRMS (ESI +ve): calculated for C20H18N3NaO4F
[M+Na]+: 406.11790. Found: 4306.11794.
in vitro Antibacterial analysis
Broth microdilution method: The minimum inhibitory
concentration (MIC) was determined according to the broth
microdilution susceptibility assay, which was described by the
National Committee of Clinical Laboratory Standards (NCCLS,
2005) with some modifications. MIC test was performed using
two-fold broth dilution method in 96 well microtitre plates.
Stock solution (1mg/mL) of each substrate and ciprofloxacin
was prepared in DMSO under aseptic conditions. The first
experimental well was filled with Mueller-Hinton broth (180
µL) and the other wells were filled with 100 µL of Mueller-
Hinton broth. A volume of 20 µL of each substance stock
solutions was added to the first well. Double-fold serial dilution
was then carried out across the plate. Overnight batch culture
of Staphylococcus aureus ATCC 6538P & 43300, Escherichia
coli ATCC 8739, Acinetobacter baumannii F24 and clinical
resistant strains of Escherichia coli 1122, 1058 & 990 (10 µL
of each microorganism′s culture) was used to inoculate the wells.
The final inoculum size obtained was about 1 × 106 cfu/mL
(prepared via viable plate count method). The plate was incu-
bated for 24 h at 37 ºC. In all assays, positive growth controls
(wells without any testing agents) and negative controls (wells
without inocula) with DMSO were performed to ensure that it
is incapable of inhibiting the growth of bacteria. MICs were
expressed as the average of two successive concentrations of
the antimicrobial agent showing no growth and growth, respec-
tively. The microorganism′s growth was detected as turbidity,
visualized by naked eyes or using a microtitre plate reader (at
630 nm) relative to an uninoculated well. MIC determination
was carried out in duplicate (in same 96 well plates) and repeated
three times for each microorganism and each tested agent.
1
1275, 1075. H NMR (500 MHz, CDCl3): δ 1.17, 1.28 (2m,
4H, H2-2′/H2-3′), 2.35 (s, 3H, CH3), 4.56 (m, 1H, H-1′), 5.81
(br s, 2H, NH2), 6.27 (d, J = 7.95 Hz, 1H, H-6′′), 6.73 (d, d, J
= 7.25, 7.3 Hz, 1H, H-4′′), 6.88 (br s, 1H, NH, exch.), 6.96 (d,
d, J = 7.55, 7.6 Hz, 1H, H-5′′), 7.12 (d, J = 7.25 Hz, 2H, H-
3′′), 7.36 (d, 3JH-F = 9.6 Hz, 1H, H-5), 8.77 (s, 1H, H-2), 15.03
(brs, 1H, COOH). 13C NMR (125 MHz, DMSO-d6): δ 10.66
(C-2′/C-3′), 18.41 (Ar-CH3), 39.89 (C-1′), 98.24 (d, 2JC-F = 23.4
Hz, C-5), 106.61 (C-3), 113.19 (C-6′′), 119.64 (C-4′′), 121.33
(d, 2JC-F = 17.2 Hz, C-7), 125.00 (C-8a), 125.47 (d, J = 9.7 Hz,
C-4a), 126.88 (C-5′′), 127.62 (C-8), 130.84 (C-3′′), 139.70 (d,
J = 4.0 Hz, C-1′′), 143.38 (C-2′′-Me), 151.09 (C-2), 157.31 (d,
1JC-F = 244 Hz, C-6), 166.29 (C(3)-CO2H), 177.34 (C-4).
HRMS: calculated for C20H19N3O3F [M+1]+: 368.14105. Found
C20H17N3O5F: 368.14120.
8-Amino-1-cyclopropyl-6-fluoro-7-[(3-methoxyphenyl)-
amino]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (22):
Faint green, yield: 98.04 % (0.15 g); m.p. 176-180 ºC (decomp.);
Rf value in system 4 = 0.26. IR (KBr, νmax, cm-1): 3487-3363,
3099, 2931, 2360, 1604, 1512, 1450, 1273, 1157, 1067, 1041.
1H NMR (300 MHz, DMSO-d6): 1.03 (m, 4H, H2-2′/H2-3′),
3.66 (s, 3H, OCH3), 4.75 (br s, 1H, H-1′), 5.53 (br s, 2H, NH2),
6.89 (s, 1H, H2′′), 6.92-7.78 (2m, 3H, Ar-H), 7.85 (br m, 1H,
H-5), 8.23 (br m, 2H, H-2), 8.75 (br s, 1H, NH, exch.), 13.52
(br s, 1H, COOH). 13C NMR (75 MHz, DMSO-d6): δ 11.22
(C-2′/C-3′), 42.25 (C-1′), 57.84 (OCH3), 107.21 (Ar-C-2′′),
109.42 (C-3), 110.01 (Ar-C-6′′), 112.22 (Ar-C-4′′), 115.32
(d, 2JC-F = 22 Hz, C-5), 122.12 (d, 3JC-F = 6.5 Hz, C-4a), 129.27
Antitumor testing
Cell lines and culture conditions:The human breast adeno-
carcinoma cell line MCF-7, human ductal breast epithelial
tumor cell line T47D, human prostate adenocarcinoma PC-3,
the human adenocarcinoma cell line Hela and human kidney
carcinomaA498 cell line, were purchased fromATCC (American
Type Culture Collection). Cell lines were cultured in high glucose
1
(Ar-C-5′′), 131.84 (d, JC-F = 16 Hz, C-7), 134.91 (C-8a),
136.23 (C-8), 141.25 (C-1′′), 150.01 (C-2), 154.51 (d, 1JC-F
=
249 Hz, C-6), 161.12 (C-3′′), 166.55 (COOH), 176.24 (d, 4JC-
= 2.0 Hz, C-4). HRMS (ESI +ve): calculated for C20H18
F
N3O4FNa [M+Na]+: 406.11790. Found: 4306.11788.

432 Al Rimawi et al.
Asian J. Chem.
Dulbecco′s modified eagle medium (DMEM) (Invitrogen, USA)
containing 10 % heat inactivated fetal bovine serum (HI-FBS)
(Invitrogen), 2 mmol L-1 of L-glutamine, 50 U mL-1 of penicillin
and 50 µg mL-1 of streptomycin. Cell lines were maintained at
37 ºC in a 5 % CO2 atmosphere of 95 % humidity.
Cell proliferation by MTT assay:Viable cell count was
determined using 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl
tetrazolium bromide (MTT) colorimetric assay as described
earlier [16]. Breifly, yellow tetrazolium dye was reduced by
active cells into purple formazan product. The quantity of form-
azan product is directly proportional to the number of living
cells in the culture.
Antiproliferative activities: The examined fluoroquino-
lones were first dissolved in a volume of DMSO to provide a
final 50 mg/mL stock solution, which was utilized to prepare
various concentrations of each compound in treatment media.
Final concentration of DMSO was maintained constant in all
treatment groups within a given experiment and never exceeded
0.1 %. To ensure exponential growth and linear relationship
between absorbance and cell number, cells were plated at a
density of 1 × 104 cells per well in 96-well culture plates. Cells
were maintained in DMEM media and allowed to adhere over-
night.After 24 h, they were treated with various concentrations,
in three triplicates for each concentration, of each compound
and incubated at 37 ºC in a 5 % CO2 incubator for 48h. At the
end of the treatment period, MTT assay was carried out as prev-
iously described [16]. Absorbance at 490 nm was read on a
plate reader (Tecan Group Ltd., Switzerland). Doxorubicin was
employed as a positive control.
fluoroquinolones were kept on the main nucleus and modifi-
cation were carried out by introducing lipophilic substituted
anilines at position 7, hoping to furnish active compounds espe-
cially against pervasive Gram-positive resistant strains. Moreover,
structural activity relationship studies (SARS) showed that C-
7 substituent has the major role on the inhibitory effect of
DNA gyrase and cell permeability and activity [18-23].
This work was designed as an extension to previously
published work by our group that aimed to prepare new fluoro-
quinolone derivatives (3-23) carrying electron donating methyl
or methoxy substitutions and to examine their biological activity
against both standard and resistant bacterial strains [24].
Synthone 2 (Scheme-I) possess an electron withdrawing C-8
nitro group to facilitate the coupling of the substituted anilines
at C-7. The antibacterial activity of nitro acids 10-16 and
reduced acids 17-23 are shown in Table-1.
All compounds, acids (10-16) and reduced (17-23) have
a good antibacterial activity against the standard Gram-positive
and Gram-negative bacterial strains. Compounds 10, 15 and
17 have shown a comparable antibacterial activity (MIC value
of 0.683, 0.39 and 0.244 µg/ml, respectively) to the reference
ciprofloxacin (MIC value of 0.439 µg/mL) against the standard
Staphylococcus aureus.
Compound 17 has shown a comparable antibacterial activity
(MIC value of 0.073 µg/mL) to the reference ciprofloxacin (MIC
value of 0.043 µg/mL) against standard Escherichia coli.Although
nitro acids (10-15) have shown good antibacterial activity against
both standard Gram-positive and Gram-negative strains, the
reduced fluoroquinolones derivatives (17-22) have shown exce-
llent antibacterial activity against both standard strains mainly
Gram positive strain. In particular, compounds 17, 18, 19, 21
and 22 were even stronger than the reference ciprofloxacin,
against standard Gram-positive strains. These data suggest that
the activity was mainly pronounced in the electron donating
reduced aniline derivatives 17, 22 that carries lipophilic meta
and para-methyl and methoxy. The lower activity exhibited by
ortho-position (20, 23) could be explained based on steric hind-
RESULTS AND DISCUSSION
Antibacterial activity: There is a continuous need to find
new antibacterial candidates with broader and/or more potent
antibacterial profile that battle the newly evolved resistant strains
[6,17]. These new derivatives 10-23 might have potential against
bacterial strains since the main active features, 6-fluoro-4-oxo-
1,4-dihydroquinoline-3-carboxylic acid, of clinically active
TABLE-1
MIC VALUES (µg/mL) FOR THE PREPARED COMPOUNDS (10-23) AGAINST TESTED BACTERIAL STRAINS*,**
S. aureus
ATCC 6538 P
S.aureus
ATCC 43300 (MRSA)
A. baumannii
E. coli ATCC
Derivative type
Reference
Compound
C-log p****
F24
8739
Ciprofloxacin
0.439
0.683
1.563
3.125
3.125
3.906
0.390
1.758
0.244
0.055
0.055
3.910
0.055
0.055
3.900
ND
4.688
18.75
2.343
18.75
ND
ND
1.172
ND
ND
ND
ND
ND
ND***
18.75
ND
ND
ND
37.5
37.5
ND
37.5
ND
50
NT***
NT
0.043
0.879
1.367
3.91
3.91
2.734
6.25
0.732
0.073
0.22
0.366
6.25
1.86
2.69
4.51
4.50
4.50
3.92
3.93
3.93
4.00
3.19
3.19
3.19
2.61
2.61
2.61
10
11
12
13
14
15
16
17
18
19
20
21
22
23
Nitro acid
derivatives
Reduced acid
derivatives
0.25
0.24
3.91
ND
ND
NT
NT
*S. aureus ATCC 6538P, MRSA 43300, E. coli ATCC 8739, A. baumannii F24 and clinical resistant strains of E. coli 1122, 1058 & 990.
**All compounds tested (14) against clinical resistant strains of E. coli 1122, 1058 & 990 have shown activity above 100 µg/mL.
***ND means antibacterial activity was above 100 µg/mL, whereas NT means antibacterial activity was not tested.
****C-log p was calculated by using Chem Draw ultra version 11.

Vol. 32, No. 2 (2020)
Antibacterial and Anticancer Properties of New Fluoroquinolones 433
rance effect of C-2 substitution. The C-8 amino group in these
series seems to provide stronger or new enzymatic interaction
through hydrogen bonding.
II enzymes, which are mediated through C3/C4 keto acid of
drug skeleton and this may explain the tolerance for structural
diversity of substituents at positions N1, C7, and C8 of quinolones
[28].
Again, these data agree with our previous assumption that
lipophilicity provided mainly by alkyl or methoxy aniline can
be preferred with compounds that work against gram positive
strains. This phenomenon was clear in present data, since most of
the compounds, in particular compounds 18, 19, 21 and 22 were
more active against Gram-positive strains.Additional H-B net-
work provided by C-8 amino group seems to play a major rule
in optimizing the antibacterial activity. In general, acid deri-
vatives (10-16) were more active against the resistant Gram-
positive strains in comparison to the reduced system (17-23).
In particular, nitro targets (10, 11, 12, 13 and 16) have shown
strong activities against the resistant Gram-positive strain (methi-
cillin resistant Staphylococcus aureus ATCC 43300, MRSA)
bearing in mind that the reference ciprofloxacin has not shown
any detectable activity against both Gram-positive resistant
strains. This is logic since that the more lipophilic quinolones
have a better ability to penetrate the lipophilic cell membrane
of Gram-positive bacteria, while less lipophilic compounds are
more liable to penetrate the cell wall of Gram-negative bacteria
[25]. In the same vein, present work reveals that most of the
compounds have low activity against clinical isolate of Gram-
negative resistant strains and this is probably due to mutations
in the genes for the bacterial targets of fluoroquinolones (DNA
gyrase [GyrA] and topoisomerase IV [ParC]) or to active efflux
of the agents via antibiotic efflux pumps [26]. In fact, all comp-
ounds tested against clinical resistant strains of E. coli 1122,
1058 & 990 have shown activity above 100 µg/mL.
Anticancer activity: There is an urgent need to explore
new promising antiproliferative activity [10]. Availability of
five cancer cell lines fortified screening these fluoroquinolones
using an in vitro cell culture system. On the other hand, the
significant co-relation between bacterial infections and cancer
might justify screening these compounds against different cancer
cell lines [27]. Recent functional studies have characterized
the role of the proposed water-metal ion bridge in mediating
quinolone-topoisomerase IV enzyme interactions. Moreover,
they demonstrate that the water-metal ion bridge is the primary
interaction between quinolones and the bacterial topoisomerase
Biological screening of cytotoxic activity against five cancer
cell lines (T47D, MCF-7, A498, HeLa and PC-3) using an in
vitro cell culture system was revealed for acid derivatives (10-
15) and reduced derivatives (17-22) in Table-2.Although most
compounds tested, have shown weak activity relative to the
positive control doxorubicin, nitro acids (10-15) were more
active than reduced derivatives (17-22). For example, compound
15 has shown reasonable activity against four different cell
lines. This could be explained through the lipophilic nature of
nitro derivatives. The average C-log p of these compounds is
higher than their corresponding reduced counterparts.
It is worth to mention that most nitro compounds displayed
growth inhibition against more than one cell line. This could
be explained through the lipophilic nature of nitro derivatives.
Also, these fluoroquinolone derivatives have similar mechanism
related to their core structure; 6-fluoro-4-oxo-1,4-dihydro-
quinoline-3-carboxylic acid. The fact that ester derivatives 3-9
showed no activity, due to loss the chelator free carboxylic acid
group, support the assumption that 4-quinolon-3-carboxylic
acid chelated core is very essential for anticancer activity. This
is further fortified by the mechanism of known quinolone anti-
cancer drug vasoroxin. It is well documented that it intercalates
DNA and inhibits topoisomerase II which leads to replication
dependant, site selective DNA damage, G2 arrest and apoptosis
[29].Yet, no clear SARS could be established from these data
against cancer cells. However, more work will be carried out
to study the chelation and lipophilic effect of these fluoroquino-
lones.
Conclusion
New fluoroquinolones (17-23) as potential antibacterial
compounds were synthesized and characterized. Their activity
was pronounced against mainly Gram-positive standard strain
and simultaneously they exhibited good activity against E. coli
standard strain. Further investigations will be carried out to
establish SAR for anticancer activity and explore their mech-
anism.
TABLE-2
IC50 VALUES (µM) OF THE TESTED FLUOROQUINOLONES ON FIVE HUMAN CANCER CELL LINES
Compound
T47D
MCF7
A498
PC-3
HeLa
373 11
296 10
219 17
380 14
321 18
297 10
319 14
313 15
334 19
370 19
375 18
260 16
336 17
241 14
166 11
332 11
179 10
10
11
12
13
14
15
17
18
19
20
21
22
234
7
198
9
250 12
203 11
200 12
153
210
7
9
259
271
8
7
162
9
179
8
205 13
289 15
299 16
307 11
337 26
180 17
315 23
237
9
393 21
422 24
397 16
485 26
453 28
432 20
410 11
450 18
389 13
479 21
409 19
399 21
430 26
471 29
424 26
444 29
352 23
362 27
339 11
294 13
280 16
307 18
373 13
255 10
Doxorubicin
3
0.8
1
0.01
1
0.01
1
0.01
2
0.1
*Values are expressed as mean SD of three experiments

434 Al Rimawi et al.
ACKNOWLEDGEMENTS
Asian J. Chem.
13. Y.M.Al-Hiari, I.S.Al-Mazari, A.K. Shakya, R.M. Darwish and R.Abu-
Dahab, Molecules, 12, 1240 (2007);
https://doi.org/10.3390/12061240.
The authors express their sincere thanks to Deanship of
Academic Research [(grant 49/2015-2016 (no.1850)] , University
of Jordan, Amman, Jordan.
14. Y.M. Al-Hiari, A.K. Shakya, M.H. Alzweiri, T.M. Al-Qirim, G. Shattat
and M.M. El-Abadelah, J. Enzyme. Inhib. Med. Chem., 26, 649 (2011);
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15. Y.M. Al-Hiari, V.N. Kasabri, A.K.Shakya, M.H. Alzweiri, F.U. Afifi,
Y.K. Bustanji and I. Al-Masri, M. Med. Chem. Res., 23, 3336 (2014);
https://doi.org/10.1007/s00044-014-0913-4.
CONFLICT OF INTEREST
The authors declare that there is no conflict of interests
regarding the publication of this article.
16. M.A. Khanfar, S.K. Bardaweel, M.R.Akl and K.A. El Sayed, Phytother.
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