Synthesis of quinoline-attached furan-2(3H)-ones having anti-inflammatory and antibacterial properties with reduced gastro-intestinal toxicity and lipid peroxidation

Article abstract of DOI:10.2298/JSC110131142A

A series of 5-aryl-3-[(2-chloroquinolin-3-yl)methylene] furan-2(3H)- ones (3a-p) were synthesized. The required 3-(substituted benzoyl)propionic acids 2a-d were prepared under Fried?l-Crafts acylation reaction conditions. The substituted 2-chloroquinoline-3-carboxaldehydes 1a-d were synthesized by reaction of substituted phenylethanone oxime with phosphorus oxychloride in presence of dimethylformamide using the Vilsmeier-Haack reaction method. These compounds were screened for their anti-inflammatory and antibacterial activities along with their ulcerogenic and lipid peroxidation potentials. The compounds that showed significant anti-inflammatory activity were further screened for their analgesic activity. The compounds were less toxic in terms of ulcerogenicity as compared to a standard, which was also supported by lipid peroxidation studies. The antibacterial activities were performed against Staphylococcus aureus and Escherichia coli. Compounds 3f, 3n and 3o showed significant activity against both S. aureus and E. coli having an minimum inhibitory concentration (MIC) value of 6.25 μg mL-1. Copyright 2011 (CC) SCS.

Full text of DOI:10.2298/JSC110131142A

J. Serb. Chem. Soc. 76 (12) 1617–1626 (2011)
JSCS–4234
UDC 547.72+547.831:615.281–
188:615.276–188
Original scientific paper
Synthesis of quinoline-attached furan-2(3H)-ones having
anti-inflammatory and antibacterial properties with reduced
gastro-intestinal toxicity and lipid peroxidation
1
1
1
*
MOHAMMAD M. ALAM , DEBA PRIYA SARKAR , ASIF HUSAIN ,
AKRANTH MARELLA1, MOHAMMAD SHAQUIQUZZAMAN1, MYMOONA
AKHTER1, MOHAMMAD SHAHARYAR1, OZAIR ALAM1 and FAIZUL AZAM2
1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard
University), New Delhi-110 062, India and 2Department of Medicinal Chemistry, Faculty of
Pharmacy, Seventh of October University, P. O. Box 2247, Misurata, Libya
(Received 31 January, revised 4 May 2011)
Abstract: A series of 5-aryl-3-[(2-chloroquinolin-3-yl)methylene] furan-2(3H)-
ones (3a–p) were synthesized. The required 3-(substituted benzoyl)propionic
acids 2a–d were prepared under Friedеl–Crafts acylation reaction conditions.
The substituted 2-chloroquinoline-3-carboxaldehydes 1a–d were synthesized
by reaction of substituted phenylethanone oxime with phosphorus oxychloride
in presence of dimethylformamide using the Vilsmeier–Haack reaction method.
These compounds were screened for their anti-inflammatory and antibacterial
activities along with their ulcerogenic and lipid peroxidation potentials. The
compounds that showed significant anti-inflammatory activity were further
screened for their analgesic activity. The compounds were less toxic in terms of
ulcerogenicity as compared to a standard, which was also supported by lipid
peroxidation studies. The antibacterial activities were performed against Sta-
phylococcus aureus and Escherichia coli. Compounds 3f, 3n and 3o showed
significant activity against both S. aureus and E. coli having an minimum
inhibitory concentration (MIC) value of 6.25 μg mL-1.
Keywords: furanone; quinoline; anti-inflammatory; analgesic; antibacterial ac-
tivity.
INTRODUCTION
Inflammation occurs due to the biosynthesis of pro-inflammatory prostaglan-
dins from arachidonic acid by the action of the enzyme cyclooxygenase (COX).
1
In the human system, COX occurs in two isoforms, viz. COX-1 and COX-2.
Constitutive, COX-1 is responsible for housekeeping functions while inducible
*Corresponding author. E-mail: drmmalam@gmail.com
doi: 10.2298/JSC110131142A
1617
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1618
ALAM et al.
COX-2 is released during tissue injury, which causes the overproduction of pros-
2
taglandins. Overexpressive COX-2 is also responsible for colon cancer.
Drugs used for treating the signs and symptoms of inflammation are referred
to as NSAIDs. However the traditional non-steroidal anti-inflamatory drugs
(NSAIDs), in addition to suppressing the effects of pathological COX also inter-
fere with the housekeeping functions of the cyclo-oxygenase enzyme, which re-
3
sults in gastrointestinal tract (GIT) irritation, bleeding and ulceration. This ex-
plains why the search for novel anti-inflammatory agent is necessary and hence,
the need to develop and screen agents which would specifically inhibit the action
of COX-2. However, this selective COX-2 inhibition has adverse cardiovascular
4
effects. Thus, there is a continuous need for the development of compounds
with a safe analgesic and anti-inflammatory profile.
Quinoline and its derivatives are an important class of pharmaceutical agents
known to occur in several natural compounds and found to possess anti-inflam-
5
6
7–10
matory and analgesic activity in addition to other pharmacological activities.
Similarly, furanone and its derivatives have been reported to have anti-inflam-
11,12
13
12,14
15,16
matory,
cardiotonic, analgesic
and COX-2 inhibition
activities in
11,12,14,20
17
18
11,12,14,19
addition to antioxidant, cytotoxic, antifungal,
and antiviral activities.
antibacterial
21
Previously, the anti-inflammatory activities of a number of 3-arylidene-5-
-(substituted phenyl)-2(3H)-furanones were studied and the results were encour-
11,12,14,22,23
aging.
In view of these observations and as a part of an ongoing re-
search program on development of newer anti-inflammatory and analgesic agents,
the synthesis and pharmacological activities of a series of 2(3H)-furanones fused
with the quinoline moiety are reported herein.
RESULTS AND DISCUSSION
Chemistry
Sixteen new compounds 3a–p were synthesized as outlined in Scheme 1.
The required 3-(substituted benzoyl)propionic acids 2a–d were prepared by
reacting different substituted benzenes with succinic anhydride in presence of an-
hydrous aluminium chloride followed by acylation under Friedel–Crafts reaction
14,22,24
conditions.
The substituted 2-chloroquinoline-3-carboxaldehydes 1a–d
were synthesized by reacting substituted phenylethanone oxime with phosphorus
oxychloride in presence of dimethyl formamide using the Vilsmeier–Haack reac-
25,26
tion method.
5-Aryl-3-[(2-chloroquinolin-3-yl)methylene] furan-2(3H)-ones 3a–p were
synthesized by condensing different aromatic aldehydes (1a–d) with a 3-(substi-
tuted benzoyl)propionic acids (2a–d) in presence of triethylamine and acetic an-
14,22
hydride under anhydrous conditions following a modified Perkin reaction.
Calculations of δ-values using incremental parameters for the hydrogen (semi-
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ANTI-INFLAMMATORY AND ANTIBACTERIAL PROPERTIES OF FURAN-2(3H)-ONES
1619
cyclic double bond) suggested the (E)-configuration. All the synthesized com-
1
13
pounds were characterized by spectroscopic data, i.e., IR, H-NMR, C-NMR
and mass, and elemental analysis. The results are given in the supplementary
material to this paper.
Scheme 1. The reaction scheme for the synthesis of compounds 3a–p (i – hydroxylamine
hydrochloride and sodium acetate; ii – dimethylformamide and POCl3; iii – anhydrous AlCl3
and succinic anhydride; iv – acetic anhydride and triethylamine).
In general, the infrared spectral data of the furanones 3a–p revealed bands at
–1
–1
–1
1790–1740 cm (lactone C=O), 1610–1560 cm (ArC=C), 1070–1060 cm
–1
1
(ArC–N) and 827–806 cm (ArC–H). In the H-NMR spectra, all the com-
pounds showed two singlets of one proton each at around δ 6.6 and 8.2 ppm,
which could be assigned to the ring β-H and the olefinic hydrogen of the aryli-
dene substituent. Other peaks were observed at the appropriate positions. Some
points could be made regarding the fragmentation pattern observed in the elec-
tron impact mass spectrum. The 5-aryl-3-[(2-chloroquinolin-3-yl)methylene] fu-
+
ran-2(3H)-ones 3a–p gave an M and M+2 (isotopic peak, due to presence of
chlorine) peak of reasonable intensities.
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ALAM et al.
Biological evaluation
Anti-inflammatory activity. The in vivo anti-inflammatory activity of the syn-
thesized compounds 3a–p was evaluated by the carrageenan-induced rat paw
27
edema method. Ibuprofen was used as the standard drug for comparison (Table
I).The anti-inflammatory activity test showed that 5-(4-bromophenyl)-3-[(2-
-chloro-6-methoxyquinolin-3-yl)methylene] furan-2(3H)-one (3o) exhibited the
maximum anti-inflammatory activity (68.9 % inhibition) in addition to 5-(4-bro-
mophenyl)-3-[(2,6-dichloroquinolin-3-yl)methylene] furan-2(3H)-one (3n), 5-(4-
methylphenyl)-3-[(2-chloro-6-methoxyquinolin-3-yl)methylene] furan-2(3H)-one
(3g) and 5-(4-bromophenyl)-3-[(2-chloro-6-methylquinolin-3-yl)methylene] fu-
ran-2(3H)-one (3p), showing 59.03, 56.62 and 53.01 % inhibition, respectively.
The results are presented in Table I.
TABLE I. Anti-inflammatory and analgesic activity along with the ulcerogenic and lipid
peroxidation effect of the synthesized compounds 3a–p
Analgesic activity
% Inhibition SEMa
Lipid peroxidationc
nmol MDA mg-1
protein
(writhing test)b
Severity
indexb
Compound
Control
No. of writhes Protection
After 2 h After 3 h
per 30 min
83±1.31
29±1.15
–
%
–
65.06
–
–
–
0.00±0.00
0.24±0.002b
0.73±0.001a
0.39±0.005ab
0.40±0.005ab
0.35±0.001ab
0.39±0.007ab
0.54±0.001ab
0.40±0.002ab
0.36±0.014ab
0.41±0.002ab
0.55±0.001ab
0.42±0.001ab
0.53±0.017ab
0.49±0.001ab
0.58±0.001ab
0.29±0.001ab
0.38±0.002ab
0.33±0.006ab
Ibuprofen 67.7±2.05 80.8±2.60 0.83±0.36
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
9.5±1.79 16.0±1.81 0.4±0.10
18.6±3.16 23.4±2.87 0.3±0.12
16.4±1.72 22.8±0.42 0.33±0.12
18.8±2.83 29.7±3.39 0.5±0.27
26.6±4.34 36.0±3.22 0.52±0.36
28±2.74 50.4±1.73 0.41±0.1
34.1±4.16 53.8±1.38 0.16±0.12
44.9±5.22 50.0±2.28 0.41±0.1
10.4±3.86 19.9±3.06 0.46±0.4
33.7±2.61 39.7±2.80 0.5±0.27
21.5±4.01 36.6±3.51 0.48±0.36
20±1.97 37.0±3.27 0.5±0.27
26.6±3.98 34.5±3.54 0.43±0.36
38.2±1.97 56.3±3.49 0.16±0.12
48.6±3.69 68.9±3.07 0.25±0.12
42.4±1.79 52.0±2.42 0.2±0.12
–
–
–
–
–
–
–
–
36±1.89
56.62
–
–
–
–
–
–
–
–
–
–
–
–
34±1.24
33±1.31
39±1.94
59.03
60.24
53.01
aRelative to the standard (ibuprofen) and data were analyzed by one-way ANOVA followed by the Tukey test
for n = 6; brelative to their respective control and the data were analyzed by one-way ANOVA followed by the
Tukey test for n = 6; clipid peroxidation activity is expressed as nmoles of MDA mg-1 protein. “±” indicates the
minimum and maximum variation in the average values. “–” indicates not tested
Based on the above observations, the following structure–activity relation-
ship can be concluded:
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ANTI-INFLAMMATORY AND ANTIBACTERIAL PROPERTIES OF FURAN-2(3H)-ONES
1621
i) presence of an electronegative group on phenyl moiety of the furanone
ring increases the anti-inflammatory activity as compared to that of an electro-
positive group;
ii) an increase in number of electropositive groups on the phenyl moiety of
the furanone ring further decreases the activity;
iii) the presence of a methoxy group on the quinoline nucleus showed
maximum activity;
iv) replacement of the methoxy group by a methyl group decreases the ac-
tivity.
All the synthesized compounds were further tested for their ulcerogenic and
lipid peroxidation effects. The test compounds (3o, 3n, 3g and 3p) that exhibited
an above 65 % ibuprofen edema inhibition were further evaluated for their anal-
gesic activity.
Analgesic activity. The analgesic activity was evaluated by the acetic acid-
28
induced writhing test. The results indicated that compounds 3o and 3n showed
60.24 and 59.03 % activity, respectively, which were comparable to that of the
standard ibuprofen (65.06 %). Compounds 3g and 3p also showed good anal-
gesic activity (Table I).
Acute ulcerogenesis. The synthesized compounds were screened for their
29
ulcerogenic activity by the Cioli et al. method. Compounds 3o and 3n showed
a severity index of 0.25±0.12 and 0.16±0.12, respectively, which were much
lower as compared to that of ibuprofen (0.83±0.36). The results indicated that the
compounds were less toxic in terms of ulcerogenicity as compared to standard,
which was also supported by lipid peroxidation studies (Table I).
Lipid peroxidation. All the compounds screened for ulcerogenic activity
30
were also analyzed for lipid peroxidation by the Ohkawa et al. method. The
–1
lipid peroxidation was measured as nmoles of malondialdehyde (MDA) mg of
protein. Ibuprofen exhibited high lipid peroxidation 0.73±0.001 whereas control
group showed 0.24±0.002. It was found that all the furanone derivatives fused
with quinoline ring showed less ulcerogenic activity along with reduced lipid
peroxidation (Table I).
Antibacterial activity. All the compounds tested for antimicrobial activity
showed inhibition of growth. Compounds 3f, 3n and 3o showed significant acti-
vity against both Staphylococcus aureus and Escherichia coli with a minimum
–1
inhibitory concentration (MIC) value of 6.25 μg mL (Table II). Of the sixteen
new compounds, two compounds, 3i and 3j were found to be more active against
–1
S. aureus with an MIC value of 6.25 μg mL . Analyses of the results indicated
that:
i) the presence of a chloro group on the quinoline nucleus induced selectivity
of the furanone towards inhibition of S. aureus;
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ALAM et al.
ii) the presence of an electropositive group on the phenyl moiety of the fura-
none ring induced inhibition of S. aureus. However, an electronegative group fa-
voured inhibition of E. coli.
TABLE II. Antibacterial activity, MIC / μg mL-1, results of the 2(3H)-furanones (the studies
were performed in triplicate)
Compound
S. aureus
E. coli
Nitrofurazone
12.5±0.0
133.37±16.67
50±0.0
133±33.34
133±33.34
25±0.0
6.25±0.0
12.5±0.0
25±0.0
6.25±0.0
6.25±0.0
25±0.0
12.5±0.0
12.5±0.0
6.25±0.0
6.25±0.0
12.5±0.0
6.25±0.0
167.67±33.34
50±0.0
50±0.0
166±33.34
50±0.0
6.25±0.0
25±0.0
50±0.0
12.5±0.0
12.5±0.0
50±0.0
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
25±0.0
12.5±0.0
6.25±0.0
6.25±0.0
25±0.0
EXPERIMENTAL
Chemistry
Chemicals were purchased from Merck and Sigma-Aldrich as synthesis grade and were
used without further purification. Melting points were determined by the open tube capillary
method and are uncorrected. The purity of the compounds was checked by thin layer chroma-
tography (TLC) on silica gel G plates (Merck No. 5544) using toluene:ethyl acetate:formic
acid (5:4:1) as the solvent system and the spots were located either under ultraviolet light or
through exposure to iodine vapour. The IR spectra were measured as potassium bromide pel-
1
lets using a Perkin-Elmer 1725X spectrophotometer. The H-NMR spectra were recorded on
Bruker spectrospin DPX-300 MHz in CDCl3 with tetramethylsilane (TMS) as an internal
standard; chemical shifts (δ) are reported in parts per million (ppm) downfield from TMS.
Mass spectra were recorded at 70 eV on a Jeol JMS-D 300 instrument fitted with a JMS 2000
data system. Spectral data are consistent with the assigned structures. Elemental analyses were
performed on a Perkin-Elmer model 240 analyzer (C, H, N) and were found within the range
of ± 0.4 % of the theoretical values.
General procedure for the synthesis of 1-(4-substituted phenyl)ethanone oximes
The 1-(4-substituted phenyl)ethanone oximes were synthesized from different substituted
acetophenones (0.1 mol), hydroxylamine hydrochloride (0.12 mol) and sodium acetate (0.12
mol) using the method reported by Cohn et al.25
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ANTI-INFLAMMATORY AND ANTIBACTERIAL PROPERTIES OF FURAN-2(3H)-ONES
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General procedure for the synthesis of the 2-chloroquinolin-3-carboxaldehydes 1a–d
To dimethylformaldehyde (0.15 mol) cooled to 0 °C, freshly distilled phosphorous oxy-
chloride (0.35 mol) was added dropwise under stirring, then the respective oxime (0.05 mol)
was added portion-wise. The reaction mixture was heated at 60 °C for 16 h. It was then
poured into ice water (300 mL) and stirred for 30 min. The 2-chloroquinoline-3-carboxalde-
hyde was filtered and recrystallized from ethyl acetate.25,26
General procedure for the synthesis of 3-(substituted benzoyl)propionic acids 2a–d
The 3-(substituted benzoyl)propionic acids were synthesized according to a previously
reported method14,22,24 using dry substituted-benzene (50 mL) under anhydrous conditions in
presence of anhydrous aluminium chloride (0.15 mol) and succinic anhydride (0.1 mol). The
obtained product was crystallized from aqueous ethanol to give a colourless compound that
gave effervescence with sodium bicarbonate.
General procedure for the synthesis of 3-[(2-chloroquinolin-3-yl)methylene]-5-(substituted
phenyl) furan-2(3H)-ones 3a–p
Each compound 2a–d (3 mmol) and each compound 1a–d (equimolar, 3 mmol) were
fused together in presence of acetic anhydride (5–8 drops) in a round-bottom flask for half an
hour. To this fused mixture, triethylamine (2 drops) was added and the heating on a heating
mantle was continued for a further 15 min. After the completion of reaction, the obtained solid
mass was crystallized from methanol and gave the desired products.
Biological evaluation
Animals. The Wistar rats and albino mice used in the present study were housed and kept
in accordance with the Hamdard University Animal Care Unit, which applies the guidelines
and rules laid down by the Committee for the Purpose of Control and Supervision of Experi-
ments on Animals (CPCSEA), Ministry of Social Justice and Empowerment, Government of
India. Wistar rats and albino mice of either sex (Hamdard University, Animal House, New
Delhi, India), weighing 180–200 g (12 weeks) and 22–25 g (8 weeks), respectively, were
used. The animals were housed in groups of six and acclimatized to ambient conditions for at
least 2 days before the experiments. Food and water were freely available up to the time of the
experiments. The food was withdrawn on the day before the experiment, but free access to
water was allowed.
Anti-inflammatory activity. The synthesized compounds were evaluated for their anti-in-
flammatory activity using the carrageenan-induced paw edema method of Winter et al.27 The
animals were randomly divided into groups of six. Group I was kept as control, and received
only 0.5 % carboxymethyl cellulose (CMC) solution. Group II was kept as the standard and
received ibuprofen. Carrageenan solution (0.1 % in sterile 0.9 % NaCl solution) in a volume
of 0.1 mL was injected subcutaneously into the sub-plantar region of the right hind paw of
each rat, 30 min after the administration of the test compounds (20 mg kg-1 p.o.) and the
standard drugs. The paw volume was measured by saline displacement shown on the screen of
digital plethysmometer (Ugo Basile) at 2 and 3 h after carrageenan injection. The edema vo-
lume in the control group (Vc) and edema volume in the groups treated with test compounds
(Vt) was measured and the percentage inhibition of edema was calculated using the formula:
Anti-inflammatory activity (% inhibition) = 100((Vc – Vt) / Vc)
where Vc is the paw volume of the control group and Vt is the paw volume of the test group.
Analgesic activity. The compounds which showed anti-inflammatory activity above 75 %
of the ibuprofen inhibition were screened for analgesic activity. The determination of the
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1624
ALAM et al.
analgesic activity was realized by the acetic acid-induced writhing method.28 Mice were
divided into groups with six in each. Group I was taken as the control and received CMC
suspension only, group II received the reference drug ibuprofen and the other groups were
treated with the test drugs (20 mg kg-1) suspended in 1.0 % CMC orally. A 1 % aqueous acetic
acid solution (0.1 mL) was used as writhing-inducing agent. The acetic acid solution was in-
jected intraperitoneally 3 h after the treatment with the reference and test drugs to the various
groups, respectively, and writhings were noted for 10–15 min after acetic acid administration.
Acute ulcerogenesis. Acute ulcerogenesis test was performed according to the method of
Cioli et al.29 Wistar rats were divided into different groups consisting of six animals in each
group. Ulcerogenic activity was evaluated after p.o. administration of test compounds or
ibuprofen at a dose of 60 mg kg-1. The control rats received p.o. administration of the vehicle
(suspension of 1 % carboxymethyl cellulose). Food but not water was removed 24 h before
administration of the test compounds. After drug treatment, the rats were fed with a normal diet
for 17 h and then sacrificed. The stomach was removed and opened along the greater
curvature, washed with distilled water and cleaned gently by dipping in normal saline. The
mucosal damage was examined by means of a magnifying glass and compared with that after
ibuprofen administration. For each stomach, the mucosal damage was assessed according to
the following scoring system: 0.5: redness, 1.0: spot ulcers, 1.5: hemorrhagic streaks, 2.0:
ulcers > 3 but < 5, 3.0: ulcers > 5.
The mean score of each treated group minus the mean score of the control group was
regarded as the severity index of gastric mucosal damage.
Lipid peroxidation. Lipid peroxidation in the gastric mucosa was determined according
to the method of Ohkawa et al.30 After screening for ulcerogenic activity, the gastric mucosa
was scraped with two glass slides and 10 % of that tissue was homogenized at 10,000 rpm in
1.8 mL of 1.15 % ice-cold KCl solution. 1 mL of suspension medium was taken from the
supernatant, 0.5 mL of 30 % trichloroacetic acid (TCA) followed by 0.5 mL of 0.8 % thiobar-
bituric acid (TBA) reagent were added to it. The tubes were covered with aluminium foil and
kept in a shaking water bath for 30 min at 80 °C. After 30 min, the tubes were taken out and
kept in ice-cold water for 10 min. These were then centrifuged at 3000 rpm for 15 min. The
absorbance of the supernatant was read at 540 nm at room temperature against the blank on a
UV spectrophotometer.
The standard curve used for estimating the concentration of MDA was prepared by using
1,1,3,3-tetraethoxypropane. The results are presented as nmol MDA mg-1 of protein.
Antibacterial activity. The antibacterial studies were performed on the synthesized com-
pounds against the microorganisms S. aureus and E. coli in meat peptone agar medium at a
concentration of 100 μg ml-1. Compounds inhibiting growth of one or more of the micro-
organisms were further tested for their MIC value. The test was performed according to the
turbidity method31 using nitrofurazone as the standard.
SUPPLEMENTARY MATERIAL
Аnalytical and spectral data of synthesized compounds are available electronically from
http://www.shd.org.rs/JSCS/, or from the corresponding author on request.
Acknowledgements. We are thankful to Mrs. Shaukat Shah, ex-in-charge of the animal
house, Jamia Hamdard, for providing the animals for the pharmacological studies and Prof. P.
K. Pillai, Head, Department of Microbiology, Majeedia Hospital, for helping in performing
the antibacterial activity tests.
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ANTI-INFLAMMATORY AND ANTIBACTERIAL PROPERTIES OF FURAN-2(3H)-ONES
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И З В О Д
СИНТЕЗА ХИНОЛИН-ВЕЗАНИХ ФУРАН-2(3Н)-ОНА КОЈИ ИМАЈУ
АНТИИНФЛАМАТОРНА И АНТИБАКТЕРИЈСКА СВОЈСТВА
УЗ СМАЊЕНУ ГАСТРОИНТЕСТИНАЛНУ ТОКСИЧНОСТ И
ЛИПИДНУ ПЕРОКСИДАЦИЈУ
MOHAMMAD M. ALAM1, DEBA PRIYA SARKAR1, ASIF HUSAIN1, AKRANTH MARELLA1, MOHAMMAD
SHAQUIQUZZAMAN1, MYMOONA AKHTER1, MOHAMMAD SHAHARYAR1, OZAIR ALAM1 и FAIZUL AZAM2
1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New
Delhi-110 062, India и 2Department of Medicinal Chemistry, Faculty of Pharmacy, Seventh of October
University, P. O. Box 2247, Misurata, Libya
Синтетисана је серија 5-арил-3-[(2-хлорохинолин-3-ил)метилен] фуран-2(3H)-она (3a–
p). Потребне 3-(супституент-бензоил)-пропионскe киселине 2a–d су добијене Friedеl–Crafts-
-овом реакцијом ациловања. Супституисани 2-хлорохинолин-3-карбалдехиди 1a–d су син-
тетисани у реакцији супституисаних фенилетанон-оксима са фосфор-оксихлоридом, у при-
суству диметил-формамида, применом Vilsmeiеr–Haack-овог реакционог метода. За ова једи-
њења је утврђивана антиинфламаторна, антибактеријска и улцерогена активност, као и спо-
собност да изазову липидну пероксидацију. Једињења која су показала значајну антиинфла-
маторну активност даље су испитивана као аналгетици. Једињења су испољила мању токсич-
ност у поређењу са стандардним препаратима, у погледу улцерогености и липидне перокси-
дације. Антибактеријска активност је тестирана спрам S. aureus и E. coli. Једињења 3f, 3n и
3o су показала значајну активност спрам обе бактерије, уз минималну инхибиторну концен-
трацију од 6,25 μg mL-1.
(Примљено 31. јануара, ревидирано 4. маја 2011)
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