Synthesis, antibacterial and cytotoxic activities of cyanoenonebenzenesulfonamide, acetamide and pyridine-3-Carbonitrile derivatives

Article abstract of DOI:10.14233/ajchem.2014.18085

A series of sulfonamides having biologically active acrylamides moieties (2, 3, 5), penta-2,4-dienamide (4), chromene-2-carboxamide (6), acetamide derivatives (7, 8) and pyridone derivative (9) were prepared. The structure of the synthesized compounds was

Full text of DOI:10.14233/ajchem.2014.18085

Asian Journal of Chemistry; Vol. 26, No. 24 (2014), 8505-8510
ASIAN JOURNAL OF CHEMISTRY
http://dx.doi.org/10.14233/ajchem.2014.18085
Synthesis, Antibacterial and Cytotoxic Activities of
Cyanoenonebenzenesulfonamide, Acetamide and Pyridine-3-carbonitrile Derivatives
1
1,*
2,3
2,*
MANSOUR S. ALSAID , MOSTAFA M. GHORAB , VICTOR KUETE , ABDELAATY A. SHAHAT1,4 and THOMAS EFFERTH
1Department of Pharmacognosy, College of Pharmacy, King Saud University. P.O. Box 2457, Riyadh 11451, Saudi Arabia
2Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, 55128 Mainz, Germany
3Department of Biochemistry, Faculty of Science, University of Dschang, Cameroon
4Phytochemistry Department, National Research Centre, 12311 Dokki, Cairo, Egypt
*Corresponding authors: Fax: +966 1 4670560; Tel: +966 534292860; E-mail: mmsghorab@yahoo.com; msalsaid@ksu.edu.sa
Received: 26 May 2014;
Accepted: 1 October 2014;
Published online: 1 December 2014;
AJC-16391
A series of sulfonamides having biologically active acrylamides moieties (2, 3, 5), penta-2,4-dienamide (4), chromene-2-carboxamide
(6), acetamide derivatives (7, 8) and pyridone derivative (9) were prepared. The structure of the synthesized compounds was verified by
elemental analyses, IR, 1H NMR and 13C NMR spectra. In addition, the structure compound 9 was confirmed through X-ray crystallography.
The antibacterial activities of all the synthesized compounds were evaluated against a panel of multi-drug resistant (MDR) Gram-negative
strains of Escherichia coli, Enterobactera erogenes, Klebsie-llapneumoniae and Pseudomonas aeruginosa whilst their cytotoxic effects
were tested against the leukemia CCRF-CEM and its adriamycin resistant subline CEM/ADR5000 cell lines. Compounds 1-5, 7 and 8
displayed or weak activities on at least one of the ten tested bacterial strains. The best MIC value of 64 µg/mL was obtained with 3 against
E. aerogenes ATCC 13048. None of the compounds displayed significant cytotoxic effect against the two studied leukemia cell line.
Nevertheless, the activity of compounds 4, 5, 8 and 9 were better than that of doxorubicin towards the resistant CEM/ADR5000 cell line.
Keywords: Novel sulfonamides, Acetamides, Pyridone, Antibacterial, Anticancer activities.
pharmacological agents possessing anticancer activity18-20. A
INTRODUCTION
large number of structurally acetamides have ultimately been
Sulfonamides are a group of compounds with known
pharmacological activities where various derivatives are used
as antibacterial1-3, antiinflammatory4, anticancer5,6 and anti-
viral7 agents. Some sulfonamides have been reported to show
anticancer activity in vitro and in vivo, including several
chromene derivatives8-11; In addition, a number of mechanisms
have been proposed to explain the anticancer activity of sulfo-
namides, the most prominent of which is inhibition of carbonic
anhydrase12-14 as suggested by Chegwidden and Spencer15.
Carbonic anhydrase is upregulated in solid tumors in response
to the hypoxic tumor microenvironment and its inhibition leads
to reduction in provision of bicarbonate which is needed to
combat the deleterious effects of a high rate of glycolytic
metabolism. Consequently, tumor growth is reduced when
carbonic anhydrase is inhibited. In addition, disruption of
microtubule assembly by sulfonamides has also been observed
and derivatives in which the NH of the sulfonamide group is
substituted by an aryl group have shown potent anticancer
activity16,17. Also, it was found that the acetamide derivatives
constitute an important class of drug, with several types of
reported to show substantial anticancer activity in vitro and in
vivo. Considering the ever-growing bacterial resistance there
is an immense need to develop new methods to treat bacterial
infections. Traditional methods of antibiotic discovery have
failed to keep pace with the evolution of this resistance. The
pilus is an organelle that is vital for the bacteria in order to
adhere to and infect host cells, as well as in establishing
biofilms. Disabling these organelles renders the bacteria
avirulent. This will at least in theory lead to more tolerated
antibiotics and hence slower development of resistance. It has
been known for several years that the ring-fused 2-pyridones
exhibit biological activity against the pili assembly machinery
in 5 uropathogenic E. coli, termed the chaperone usher
pathway. The chaperone usher pathway is a complex cascade
reaction which occurs in the periplasm of Gram-negative
bacterium. There are many different types of pili, of which
the Type 1 and P-pili involved in the infection of bladder cells
and kidneys are the most studied. Pili are built up from
repeating protein subunits; these subunits are called Pap in
P-pili and Fim in Type 1 pili. One of the key proteins in the

8506 Alsaid et al.
Asian J. Chem.
assembly of P pili is the chaperone PapD, which is responsible
for the delivery of the pili building blocks from the surface of
the inner membrane to the assembly area located at the outer
membrane. The 2-pyridone core is an interesting heterocycle
which is common to many natural products (Fig. 1) as well as
synthetic compounds, which possesses wide spread biological
characteristics. The 2-pyridone core is also present in registered
pharmaceuticals for instance Corotrop® and Primacor® both
are used in the treatment of heart failure. The active ingredient
in these drugs is the 2-pyridone based compound milrinone
(Fig. 1), which is a phosphodiesterase inhibitor. Sebiprox®,
used in treatment of dandruff, also contains a 2-pyridone
based active ingredient called ciclopirox (Fig. 1). Compounds
containing heteroaromatic rings frequently play an important
role as scaffolds of bioactive substances. It is well known that
pyridone and its derivatives are among the most popular N-
heteroaromatic compounds integrated into the structures of
many pharmaceutical compounds and their structural units
occur in various molecules exhibiting diverse biological
activities21-25. Based on the above information and as a conti-
nuation of our previous work on anticancer26-28, we report the
synthesis of sulfonamides, acetamides and 2-pyridone deri-
vative which is expected to exhibit antibacterial and anticancer
activities.
spectrometer (Bruker, Flawil, Switzerland, δ ppm) at 500 MHz,
using TMS as internal standard. Elemental analyses were
performed on Carlo Erba 1108 Elemental Analyzer (Heraeus,
Hanau, Germany). All compounds were within 0.4 % of the
theoretical values.
Synthesis of benzenesulfonamide derivatives (1-6):
2-cyano-N-(4-sulfamoylphenyl) acetamide (1). Compound 1
was prepared according to reported method 29.
2-Cyano-3-(4-substituted)-N-(4-sulfamoylphenyl) acryl-
amides (2-5)
General procedure: A mixture of 1 (2.11 g, 0.01 mol)
and aromatic aldehydes (0.012 mol) in absolute ethanol (20
mL) containing piperidine (0.5 mL) was refluxed for 4 h. The
obtained solid was filtered while hot and crystallized from
dioxane to give 2-5, respectively.
2-Cyano-3-(4-fluorophenyl)-N-(4-sulfamoylphenyl)
acrylamide (2): Yield % 83; m.p. 265.9 °C; IR (KBr, νmax
,
cm-1): 3337, 3310, 3290 (NH, NH2), 3065 (CH arom.), 2966,
2876 (CH aliph.), 2205 (C≡N), 1685 (C=O), 1396, 1184 (SO2):
1H NMR in (DMSO-d6) δ: 7.0-8.1 [m, 9H, Ar-H + SO2NH2],
8.3 [s, 1H, CH]. 10.9 [s, 1H, NH, D2O exchangeable]. 13C
NMR in (DMSO-d6): 105.6, 114.3 (2), 114.9, 122.6 (2) 126.7
(2), 127.8 (2), 129.9, 130.8, 133.7, 152.6, 163.1, 164.9. Anal.
Calcd; for C16H12N3O3S (345.35): C, 55.65; H, 5.50; N, 12.17;
found: C, 55.38; H, 5.22; N, 12.51.
EXPERIMENTAL
2-Cyano-3-(2,4-dinitrophenyl)-N-(4-sulfamoylphenyl)-
Melting points (°C, uncorrected) were determined in open
capillaries on a Gallenkemp melting point apparatus (Sanyo
Gallenkemp, Southborough, UK). Pre-coated silica gel plates
(silica gel 0.25 mm, 60 G F 254; Merck, Germany) were used
for thin layer chromatography, dichloromethane/methanol
(9.5:0.5 mL) mixture was used as a developing solvent system.
IR spectra were recorded in KBr discs using IR-470 Shimadzu
spectrometer (Shimadzu, Tokyo, Japan). NMR spectra in
(DMSO-d6) were recorded on BrukerAc-500 ultra-shield NMR
acrylamide (3): Yield % 88; m.p. 215.6 °C; IR (KBr, νmax
,
cm-1): 3416, 3372, 3286 (NH, NH2), 3096 (CH arom.), 2976,
2836 (CH aliph.), 2218 (C≡N), 1696 (C=O), 1378, 1161 (SO2).
1H NMR in (DMSO-d6); δ: 7.1-8.4 [m, 9H, Ar-H + SO2NH2],
8.7 [s, 1H, CH], 11.3 [s, 1H, NH; D2O-exchangeable]. 13C
NMR in (DMSO-d6): 109.0, 116.7, 118.8, 120.6 (2), 128.1
(2), 128.7, 130.8, 135.9, 138.4, 141.2, 146.7, 150.1, 155.2,
165.3. Anal. Calcd; for C16H11N5O7S (417.35): C, 46.05; H,
2.66; N, 16.78; found: C, 46.36; H, 2.43; N, 16.47.
HO
O
OH
O
OH
N
CN
N
H2N
OH
O
N
H
O
O
HO
O
Tyrphostin AG 99
Camptothecin
Pretenellin B
N
N
O
CN
N
NH
N
O
N
O
H
OH
Cytisin
Ciclopirox
Milrinone
Fig. 1. Examples of naturally occurring 2-pyridones, together with two examples of 2-pyridone based compounds incorporated in registered pharmaceuticals

Vol. 26, No. 24 (2014)
Synthesis of Cyanoenonebenzenesulfonamide, Acetamide and Pyridine-3-carbonitrile Derivatives 8507
2-Cyano-5-[4-(dimethylamino)-N-(4-sulfamoylphenyl]-
penta-2,4-dienamide (4): Yield % 89; m.p. 240.2 °C; IR (KBr,
νmax, cm-1): 3360, 3315, 3272 (NH, NH2), 3091 (CH arom.),
2946, 2860 (CH aliph.), 2212 (C≡N) 1676 (C=O), 1377, 1156
(SO2). 1H NMR in (DMSO-d6); δ: 3.0 [s, 6H, N(CH3)2], 6.6,
6.9 [2d, 2H, CH=CH; J = 7.0, 7.1 Hz], 7.5 [s, 1H, CH], 7.7-
8.0 [m, 10H, Ar-H + SO2NH2], 10.3 [s, 1H, NH; D2O-
exchangeable]. 13C NMR in (DMSO-d6): 40.1 (2), 96.7, 112.4
(2), 115.8,122.1 (2),122.8, 126.4, 126.8 (2), 129.3 (2), 130.6,
138.9, 141.5, 149.7, 164.2. Anal. Calcd; for C20H20N4O3S
(396.46): C, 60.59; H, 5.08; N, 14.13; found: C, 60.31; H,
5.37, N, 13.84.
(0.5 mL) were refluxed for 5 h. The reaction mixture was
triturated with ethanol and the solid obtained was recrystallized
from ethanol to give compound 930.
X-Ray analysis: A single-crystal suitable for an X-ray
structural analysis was obtained by slow evaporation from an
ethanolic solution at room temperature. Compound 9 (Fig. 2),
the 1,2-dihydropyridine ring (N1/C1-C5) is essentially planar
with a maximum deviation of 0.021 (1)A at atom N1 and almost
perpendicular with the benzene ring (C6-C11) with a dihedral
angle of 85.33 (8)°. Bond lengths and angles are within the
normal ranges and are comparable to those in the related
structures34,35. The crystal structure is shown in (Fig. 3). The
molecules are linked into a one-dimensional chain along the
b-axis via C4-H4A·O1 interactions30.
3-(4-Bromophenyl)-2-cyano-N-(4-sulfamoylphenyl)-
acrylamide (5): Yield % 79; m.p. 233.5 °C; IR (KBr, νmax
,
cm-1): 3390, 3309, 3287 (NH, NH2), 3100 (CH arom.), 2992,
2920 (CH aliph.), 2219 (C≡N) 1689 (C=O), 1336, 1156 (SO2).
1H NMR in (DMSO-d6); δ: 7.0-7.9 [m, 10H,Ar-H + SO2NH2],
8.4 [s, 1H, CH], 11.2 [s, 1H, NH, D2O-exchangeable]. 13C NMR
in (DMSO-d6): 108.2, 115.1, 119.8 (2), 121.7, 128.4 (2), 129.6
(2), 130.7 (2), 133.8, 136.7, 140.8, 155.1, 164.6. Anal. Calcd;
for C16H12BrN3O3S (406.25): C, 47.30; H, 2.98; N, 10.34;
found: C, 47.67; H, 2.65; N, 10.08.
Antibacterial assay: The studied microorganisms
included reference (ATCC) and multidrug resistant strains of
Pseudomonas aeruginosa (PA01, PA124), Klebsiella pneumoniae
(ATCC11296, KP55), Escherichia coli (ATCC8739,AG100ATet,
AG102) and Enterobacter aerogenes (ATCC-13048, CM64,
EA289) obtained from theAmerican Type Culture Collection.
Their bacterial feature was previously reported36. They were
maintained on agar slant at 4 °C and sub-cultured on a fresh
Mueller-Hinton Agar plates 24 h prior to any antimicrobial
test37. The Mueller Hinton Broth (MHB) was used for the
minimal inhibitory concentration (MIC) determinations.
Chloramphenicol (Sigma-Aldrich, St. Quentin Fallavier,
France) was used as reference antibiotics (RA) respectively
against bacteria. p-Iodonitrotetrazolium chloride (INT, Sigma-
Aldrich) was used as microbial growth indicator. The MIC
determinations on bacteria was conducted using rapid INT
colourimetric assay according to described methods38 with
some modifications. Briefly, the test sample was first of all
dissolved in 10 % (v/v) DMSO/MHB to give a final concen-
tration of 512 µg/mL and serially diluted twofold to obtain
concentration ranges. 100 µL of each concentration was added
in a well (96-well microplate) containing 95 µL of MHB and
5 µL of inoculum (standardized at 1.5 × 106 CFU/mL by adjus-
ting the optical density to 0.1 at 600 nm SHIMADZU UV-
120-01 spectrophotometer)39. The final concentration of DMSO
in the well was less than 3 % (preliminary analyses with 3 %
(v/v) DMSO do not alter the growth of the test organisms).
The negative control well consisted of 195 µL of MHB and
5 µL of the standard inoculum40. The plates were covered with
a sterile plate sealer, then agitated to mix the contents of the
wells using a plate shaker and incubated at 37 °C for 18 h.
The assay was repeated three times in triplicate. The MIC of
samples was detected following addition (40 µL) of 0.2 mg/mL
p-iodonitrotetrazolium chloride and incubation at 37 °C for
0.5 h37. Viable microorganisms reduced the yellow dye to a
pink colour. MIC was defined as the lowest sample concen-
tration that prevented this change and exhibited complete
inhibition of bacterial growth41.
3-Oxo-N-(4-sulfamoylphenyl)-3H-benzo[f]chromene-
2-carboxamide (6): To a solution of 1 (2.11 g, 0.01 mol) in
acetic anhydride (15 mL), 2-hydroxy-1-naphthaldehyde
(1.72 g, 0.01 mol) and fused sodium acetate (0.8 g, 0.01 mol)
was added. The reaction mixture was heated under reflux for
2 h and the obtained solid was crystallized from acetic acid to
give compound 6.
Yield 79 %; m.p. 287.1 °C; IR (KBr, νmax, cm-1): 3343,
3309, 3275 (NH, NH2), 3076 (CH arom.), 1700, 1673 (2C=O),
1
1374, 1184 (SO2). H NMR in (DMSO-d6); δ: 7.4- 8.1 [m,
12H,Ar-H + SO2NH2], 8.5 [s, 1H, CH], 10.3 [s, 1H, NH, D2O-
exchangeable]. 13C NMR in (DMSO-d6): 116.3, 116.9, 118.2,
120.7 (2), 121.4, 122.6, 125.2, 127.3 (2), 128.2 (2), 131.7 (2),
135.7 (2), 142.6, 154.8, 168.9, 172.0. Anal. Calcd; for
C20H14N2O5S (394.40): C, 60.91; H, 3.58; N, 7.10; found: C,
61.13; H, 3.81; N, 7.42.
2-Cyano-N-(2-ethylphenyl) acetamide (7): A mixture
of 2-ethylaniline (1.21 g, 0.01 mol) and ethyl cyanoacetate
(1.13 g, 0.01 mol) was fused at 220 °C for 3 h. The reaction
mixture was concentrated and cooled. The obtained product
was crystallized from ethanol to give compound 733.
2- Cyano-N-(3-ethylphenyl) acetamide (8): A mixture
of 3-ethylaniline (1.21 g, 0.01 mol) and ethyl cyanoacetate
(1.13 g, 0.01 mol) was fused at 220 °C for 3 h. The reaction
mixture was concentrated and cooled. The obtained product
was crystallized from ethanol to give compound 833.
Yield, 88 %, m.p. 86-88 °C; IR (KBr, νmax, cm-1): 3317
(NH), 3100 (CH. arom.), 2960, 2870 (CH aliph.), 2260 (C≡N),
1670 (C=O). 1H NMR spectrum of 3 in (DMSO-d6) δ : 1.2 [t,
3H, CH3], 2.6 [q, 2H, CH2], 3.6 [s, 2H, CH2], 4.2 [s, 1H, NH,
exchangeable with D2O], 7.03-7.7 [m, 4H,Ar-H]. Anal. Calcd;
for C11H12N2O: C, 70.21; H, 6.38, 14.89; found: C, 70.50; H,
6.10; N, 14.60.
Cytotoxicity: The resazurin reduction assay42 was perfor-
med to assess the cytotoxicity of the synthesized compounds
and doxorubicin towards various sensitive leukemia CCRF-
CEM cells and its adriamycin resistant subline CEM/ADR5000.
The assay is based on the reduction of the indicator dye, resa-
zurin, to the highly fluorescent resorufin by viable cells. Non-
viable cells rapidly lose their metabolic capacity to reduce
1-(3-Ethylphenyl)-4,6-dimethyl-2-oxo-1,2-dihydropy-
ridine-3-carbonitrile (9): A mixture of 2-cyano-N-(3-ethyl-
phenyl)acetamide 3 (1.88 g, 0.01 mol) and acetylacetone (1 g,
0.01 mol) in absolute ethanol (50 mL) containing piperidine

8508 Alsaid et al.
Asian J. Chem.
H
N
resazurin and, thus, do not produce fluorescent signals
anymore. aliquots of 2 × 104 cells per well were seeded in 96-
well-plates in a total volume of 100 µL. The studied compound
was immediately added in varying concentrations in an
additional 100 µL of culture medium to obtain a total volume
of 200 µL/well. After 72 h, resazurin (Sigma-Aldrich,
Schnelldorf, Germany) (20 µL, 0.01 % w/v) in double distilled
H2O was added to each well and the plates were incubated at
37 °C for 4 h. Fluorescence was measured on an Infinite M2000
ProTM plate reader (Tecan, Crailsheim, Germany) using an
excitation wavelength of 544 nm and an emission wavelength
of 590 nm. Each assay was done at least twice with six repli-
cates each. The viability was evaluated based on a comparison
with untreated cells. IC50 values represent the compound
concentrations required to inhibit 50 % of cell proliferation
and were calculated from a calibration curve by linear regre-
ssion using Microsoft Excel.
O
NH2
CN
O
CN
O
Fusion
R1
R1
R2
R2
7
8
, R1= C2H5, R2= H
, R1= H, R2= C2H5
CN
O
7
O
O
Dioxane
TEA
N
(9)
Scheme-II: Formation of acetamide and pyridone derivatives (7-9)
RESULTS AND DISCUSSION
cm-1, in addition to a carbonyl absorption band in the region
1696-1676 cm-1, absorption bands due to C=N in the region
2219- 2205 cm-1 and SO2 functions in the region 1396-1156
cm-1. 1H NMR spectra of compounds 2-5 in (DMSO-d6) revealed
a singlet in the region 10.3-11.3 ppm corresponding to a NH
group. Also, interaction of compound 1 with 2-hydroxy-1-
naphthaldehyde in acetic anhydride containing anhydrous
sodium acetate furnished the corresponding 3-oxo-N-(4-
sulfamoylphenyl)-3-H-benzo[f]chromene-2-carboxamide (6).
The structure of compound 6 was confirmed on the basis of
elemental analysis and spectral data. IR spectrum showed
bands at 3343, 3309, 3275 cm-1 (NH, NH2), 1700, 1673 cm-1
(2C=O), 1374, 1184 (SO2). 1H NMR spectrum in (DMSO-d6)
revealed signals at 8.5 ppm due to the CH group of chromene
and 10.3 ppm corresponding to a NH group. Interaction of
2-ethyl or 3-ethylaniline with ethyl cyanoacetate furnished the
The aim of this work was to design and synthesis of a
series of sulfonamides having the biologically active cyano
enone Michael acceptor moiety (2-5), benzochromene (6),
acetamides (7, 8) and pyridine (9) (Scheme I and II) and evalu-
ation of their antibacterial and anticancer activities. 2-Cyano-
N-(4-sulfamoylphenyl) acetamide (1)29, is a highly reactive
intermediate extensively used for synthesis of heterocyclic
compounds. Thus, condensation of compound 1 with aromatic
aldehydes in refluxing absolute ethanol in the presence of a
catalytic amount of piperidine afforded the corresponding
sulfonamide derivatives (2-5), respectively, (Scheme-1). The
structures of the later products were assigned on the basis of
their analytical and spectral data. The IR spectra of the reaction
products showed in each case four absorption bands corres-
ponding to NH, NH2 functions in the region 3416-3272
CHO
O
CN
OH
O
RCHO
H2N
S
NH
Ac2O/ NaOAc
EtOH/Pip
O
( 1 )
O
O
R
O
S
O
NH
O
H2N
H2N
NH
CN
S
O
O
O
( 6 )
R=
O2N
Br
N
F
NO2
(5)
(2)
(4)
(3)
Scheme-I: Synthesis of benzenesulfonamide derivatives (1-6)

Vol. 26, No. 24 (2014)
Synthesis of Cyanoenonebenzenesulfonamide, Acetamide and Pyridine-3-carbonitrile Derivatives 8509
corresponding acetamide derivatives 7 and 8, respectively. The
structure of compounds 7 and 8 was proved in the basis of
elemental analysis and spectral data. The corresponding pyridone
derivative 9 was obtained via reaction of compound 8 with
acetylacetone in the presence of acatalytic amount of piperedine.
The structure of compound 9 was established by elemental
analysis, spectral data. In addition the structure compound 9 was
confirmed through X-ray crystallography30 (Figs. 2, 3).
Fig. 3. A crystal packing diagram of compound 8 viewed along the c axis.
For the sake of clarity, H atoms not involved in the intermolecular
interactions (dashed lines) have been omitted
the compounds displayed significant activities (IC50 values
below 10 µM)32 against the two studied leukemia cell line
(Table-2). Nevertheless, the activity of compounds 4, 5, 8 and
9 (IC50 < 40 µg/mL) were better than that of doxorubicin
towards the resistant CEM/ADR5000 cell line.
TABLE-2
CYTOTOXICITY OF THE SYNTHESIZED COMPOUNDS AND
DOXORUBICIN LEUKEMIA CCRF-CEM AND CEM/ADR5000
CELL LINES AS DETERMINED BY THE RESAZURIN
REDUCTION ASSAY
Leukemia cell line and IC50 values (µg/mL)
Compound
CCRF-CEM
> 40
CEM/ADR5000
> 40
1
> 40
> 40
2
> 40
> 40
3
> 40
> 40
> 40
37.83 0.88
38.60 1.22
> 40
4
5
6
> 40
> 40
7
37.67 2.94
> 40
0.13 0.01
38.91 1.28
33.13 7.23
106.05 7.77
8
9
Doxorubicin
Fig. 2. Molecular structure of compound 8, showing 30 % probability
displacement ellipsoids and the atom-numbering scheme
Conclusion
Biological activity: The results of the antibacterial assays
(Table-1) indicated that compounds 1-5, 7 and 8 displayed
moderate (10 < MIC < 100) or weak (100 < MIC < 625) activi-
ties31 on at least one of the ten tested bacterial strains (Table-1).
No activity was observed with compounds 6 and 9. The best
MIC value of 64 µg/mL was obtained with 3 against E. aerogenes
ATCC 13048. However, none of the studied compounds was
as active as choramphenicol. In cytotoxicity as says, none of
The objective of the present study was to synthesize and
evaluate the antibacterial and anticancer activities of some
sulfonamide, benzochromene, acetamide and pyridone
derivatives. Though none of the studied compound displayed
significant antibacterial or cytotoxic activities, some of them
such as 3 (against bacteria) as well as 4, 5, 8 and 9 (against
cancer cell line) could serve as lead molecules to synthesize
new derivative with promising effects.
TABLE-1
MINIMAL INHIBITORY CONCENTRATION (MIC) OF THE SYNTHESIZED COMPOUNDS
AND CHLORAMPHENICOL ON THE STUDIED MICROORGANISMS
Microorganisms and MIC (µg/mL)
Compound
E. coli
E. aerogenes
K. pneumoniae
ATCC11296 KP55
P. aeruginosa
PA01 PA124
ATCC8739 AG100ATet
AG102
512
128
ATCC13048 EA-CM64 EA289
> 512
> 512
128
> 512
> 512
> 512
> 512
> 512
> 512
2
> 512
> 512
128
> 512
> 512
> 512
> 512
512
> 512
> 512
64
> 512
> 512
> 128
> 512
> 512
> 512
> 512
> 512
> 512
> 256
> 512
> 512
> 128
> 512
> 512
> 512
> 512
> 512
> 512
256
> 512
> 512
128
> 512
512
128
> 512
512
128
> 512
> 512
> 512
> 512
> 512
> 512
32
512
> 512
> 128
> 512
> 512
> 512
512
1
2
128
3
> 512
> 512
> 512
512
512
> 512
16
128
256
256
4
> 512
> 512
> 512
> 512
> 512
8
512
> 512
> 512
> 512
> 512
> 512
64
5
6
> 512
> 512
> 512
> 512
4
7
> 512
> 512
64
8
> 512
32
9
CHL
CHL: Chloramphenicol

8510 Alsaid et al.
ACKNOWLEDGEMENTS
Asian J. Chem.
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The authors are grateful to the sponsorship of the Research
Center, College of Pharmacy and the Deanship of Scientific
Research, King Saud University, Riyadh, Saudi Arabia.
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