New amides of sulphonamides: Synthesis and biological evaluation

Article abstract of DOI:10.4067/S0717-97072010000100017

A series of amide-derivatives has been synthesized by establishing an amide linkage (-CONH-) between appropriate sulphonamide moiety and different 3-(4-substituted-benzoyl) propionic acids through one-pot reaction. The structures of the newly synthesized compounds were established on the basis of modern analytical techniques. These amides were evaluated for their antiinflammatory, ulcerogenic and antibacterial activities. Some of the compounds showed good antiinflammatory activity. Additionally, these derivatives were very low in their ulcerogenic action.

Full text of DOI:10.4067/S0717-97072010000100017

J. Chil. Chem. Soc., 55, Nº 1 (2010)
NEW AMIDES OF SULPHONAMIDES: SYNTHESIS AND BIOLOGICAL EVALUATION
ASIF HUSAIN1*, AUSAF AHMAD2, M. MUJEEB3, MYMOONA AKHTER1
1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi- 110 062, India; 2Department of
Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY 14642, USA; 3Department of Pharmacognosy & Phytochemistry, Faculty
of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi- 110 062, India
(Received: April 13, 2009 - Accepted: December 17, 2009)
SUMMARY
A series of amide-derivatives has been synthesized by establishing an amide linkage (-CONH-) between appropriate sulphonamide moiety and different
3-(4-substituted-benzoyl) propionic acids through one-pot reaction. The structures of the newly synthesized compounds were established on the basis of modern
analytical techniques. These amides were evaluated for their antiinflammatory, ulcerogenic and antibacterial activities. Some of the compounds showed good
antiinflammatory activity. Additionally, these derivatives were very low in their ulcerogenic action.
Keywords: Amide, antiinflammatory, sulphonamide, antibacterial.
chloride (0.1125 moles). The reaction mixture was refluxed under anhydrous
conditions for two hours and after completion of the reaction excess solvent
was removed by steam distillation. On cooling, a solid mass separated out
which was filtered and purified by dissolving in sodium hydroxide solution,
filtering, followed by addition of hydrochloric acid. The solid mass so obtained
was filtered, washed with cold water, dried and recrystallized from methanol
to give 1-4.
INTRODUCTION
The gastrointestinal toxicity of acidic non-steroidal antiinflammatory drugs
(NSAIDs) is one of the most challenging problems in medicinal chemistry1.
NSAIDs form a class of therapeutic agents that are most widely used world
over because of their antiinflammatory, analgesic and antipyretic effects.
3-(4-Substituted benzoyl)propionic acids belong to well known aroylpropionic
acid class of non steroidal antiinflammatory agents. Aroylpropionic acids are
effective antiinflammatory agents and some of them are available in the market,
however, they are associated with gastrointestinal side effects; a common
3-(4-Chlorobenzoyl)propionic acid (1). Yield 72%; M.p. 124° C. 1H-NMR
(CDCl3, δ, ppm): 2.81 & 3.38 (t, e, 2x -CH2-), 7.45 & 7.92 (d, each, A2B2,
p-substituted phenyl).
feature of NSAIDs2-4
. Studies suggest that the direct tissue contact of these
agents plays an important role in the production of side effects and the reported
3-(4-Methoxybenzoyl)propionic acid (2). Yield 88%; M.p. 152° C.
1H-NMR (CDCl3, δ, ppm): 2.80 & 3.28 (t, e, 2x -CH2-) 3.88 (s, 3H, -OCH3),
6.94 & 7.97 (d, each, A2B2, p-substituted phenyl).
literature confirms that gastrointestinal side effects of aroylpropionic acids are
3-(4-Methylbenzoyl)propionic acid (3). Yield 66%; M.p. 106° C. 1H-NMR
(CDCl3, δ, ppm): 2.65 & 3.26 (t, e, 2x -CH2-) 2.37 (s, 3H, -CH3), 7.27 & 7.85
(d, each, A2B2, p-substituted phenyl).
due to presence of free carboxylic group in the parent drug3,4
.
Sulphonamides are one of the least expensive drugs and this factor largely
accounts for their greater extent of use in developing countries like India. They
are used in urinary tract infections, meningitis, streptococcal pharyngytis,
bacillary dysentery, trachoma, cancroids, malaria, toxoplasmosis, nocardiasis
and conjunctivitis5-7. Dapsone still remains the drug of choice for all forms of
leprosy. They are generally taken orally in higher doses which cause nausea,
vomiting and epigastric pain7.
1
3-(4-Ethylbenzoyl)propionic acid (4). Yield 75%; M.p. 110° C. H-NMR
(CDCl3, δ, ppm): 1.25 (t, 3H, CH CH2-), 2.69 (q, 2H, CH3CH2-), 2.80 & 3.30 (t,
each, 2x -CH2-), 7.27 & 7.90 (d, 3each, A2B2, 4H, p-substituted phenyl).
General procedure for the synthesis of amides (5-14)
Amides were synthesized by dissolving 3-(4-substituted-benzoyl)
There are conditions when an inflammation occurs in response to a
microbial infection, and a combination of the antiinflammatory drug with
antimicrobial agent is prescribed in such conditions. These combinations
often cause side effects because of high doses of drugs. Searching for new
compounds, which would combine two activities seem to be promising way
to overcome that problem8. In view of these points and in continuation of our
work on novel amides9,10, It was considered worthwhile to study various amide-
derivatives of sulphonamides with 3-aroylpropionic acids in order to improve
their efficacy and to decrease side effects.
propanoic acid (1-4) (0.001 mol) and sulfanilamide
/ sulfadiazine /
sulfamethoxazole / isoniazid (0.001 mol) or dapsone (0.0005 mol) in minimum
quantity of dry pyridine separately. The two solutions were then mixed together
and stirred magnetically followed by the addition of phosphorous oxychloride
(0.9ml) drop wise while maintaining the temperature below 5 °C. The contents
were stirred for another half-hour and left overnight. The reaction mixture was
then poured into ice cold water and a solid mass, which separated out, was
filtered, washed, dried and crystallized from ethanol to give 5-14 (Table 2).
N1-[4-(2-Pyrimidinylsulfamoyl)phenyl]-4-(4-chlorophenyl)-4-
1
oxobutanamide (5): Yield: 54 %; m.p. 166-168 °C; H-NMR (DMSO-d , δ,
EXPERIMENTAL
ppm): 2.84 & 3.36 (t, each, 2x -CH2-), 6.94 (t, 1H, H-4, diazine ring), 7.256(m,
2H, H-3,5, diazine ring), 7.73 & 8.31 (d, each, A2B , p-substituted phenyl ring),
7.87 & 7.95 (d, each, A2B2, 4H, p-chlorobenzene rin2 g), 10.03 (s, 1H, -CONH-);
MS (m/z): 444 (M+), 380, 234, 195, 139, 77; Anal. C H17Cl N4O4S, calcd. C,
54.00; H, 3.85; N, 12.59; found C, 54.12; H, 3.76; N, 2102.52.
Chemistry
Melting points were determined in open capillary tubes and are uncorrected.
Purity of the compounds was checked by thin layer chromatography (TLC) on
silica gel G plates, with the solvent system: toluene-ethyl acetate-formic acid
(5:4:1, v/v/v). The spots were located under iodine vapours and UV light.
Elemental analyses were performed on a Perkin-Elmer 240 analyzer and the
values were in range of ±0.4% for each element analyzed (C, H, N). 1H-NMR
spectra were recorded on Varian E-360 MHz or Bruker spectropsin DPX-
300MHz with tetramethylsilane (TMS) as an internal standard. The splitting
pattern abbreviations are as follows: s, singlet; d, doublet; dd, double doublet;
t, triplet; q, quartet; m, multiplet. Mass spectra were recorded on a Jeol JMS-D
300 instrument fitted with a JMS 2000 data system at 70 eV. The progress
of the reactions was monitored on silica gel G plates using iodine vapors as
visualizing agent.
N1-[4-(5-Methyl-3-isoxazolylsulfamoyl)phenyl]-4-(4-chlorophenyl)-
1
4-oxobutanamide (6): Yield: 62 %; m.p 179-180 ° C; H-NMR (DMSO-d6,
δ, ppm): 2.32 (s, 3H, -CH ), 2.81 & 3.53 (t, each, 2x -CH2), 6.18 (s, 1H,
methoxazole ring), 7.29 & 73.87 (d, each, A2B , 4H, p-chlorobenzene ring), 7.44
& 7.91 (d each, A2B2, 4H, p-substituted phe2nyl ring), 9.98 (s, 1H, -CONH-);
MS (m/z): 447 (M+), 383, 237, 139, 77; Anal. C H Cl N3O5S, calcd. C, 53.63;
H, 4.05; N, 9.38; found C, 53.45; H, 4.12; N, 9.2304.18
N1-(4-Sulfamoylphenyl)-4-(4-methoxyphenyl)-4-oxobutanamide
(7):
Yield: 60 %; m.p 168° C; 1H-NMR (DMSO-d6, δ, ppm): 2.64 (s, 3H, -OCH3),
2.87 & 3.51 (t, each, 2x -CH2-), 6.86 (s, 2H, -SO2NH ), 7.56 & 7.83 (d,
each, A2B2, 4H, p-substituted phenyl ring), 7.73 & 7.97 (2d, each, A2B2, 4H,
p-anisole ring), 10.11 (s, 1H, -CONH-).; MS (m/z): 362 (M+), 190, 135, 107;
Anal. C17H18N2O5S, calcd. C, 56.34; H, 5.01; N, 7.73; found C, 56.42; H, 5.05;
Preparation of 3-(4-substituted benzoyl)propionic acid (1-4)
Succinic anhydride (0.1 mole) was reacted with an appropriate aromatic
compound (substituted benzene; 50 mL) in presence of anhydrous aluminium
e-mail: drasifhusain@yahoo.com
74

J. Chil. Chem. Soc., 55, Nº 1 (2010)
N, 7.58.
N1-[4-(2-Pyrimidinylsulfamoyl)phenyl]-4-(4-methoxyphenyl)-4-
standard drugs. The paw volume was measured by saline displacement shown
on screen of digital Plethysmometer at 2 and 3 hrs after carrageenan injection.
Thus the edema volume in control group (Vc) and edema volume in groups
treated with test compounds (Vt) was measured and the percentage inhibition
of edema was calculated using the formula:
oxobutanamide (8): Yield: 58 %; m.p. 154 °C; 1H-NMR (DMSO-d , δ, ppm):
2.54 (s, 3H, -OCH3), 2.83 & 3.34 (t, each, 2x -CH2-), 6.92 (t, 1H, H6-4, diazine
ring), 7.26 (m, 2H, H-3, 5, diazine ring), 7.68 & 8.04 (d, each, A B , 4H,
p-substituted phenyl ring), 7.76 & 7.95 (d, each, A2B2, 4H, p-aniso2le 2ring),
9.53 (s, 1H, -CONH-).; MS (m/z): 440 (M+), 358, 234, 190, 135, 77; Anal.
C21H20N4O5S, calcd. C, 57.26; H, 4.58; N, 12.72; found C, 57.08; H, 4.61; N,
12.65.
Antiinflammatory activity (% inhibition) = [(Vc-Vt)/Vc]x100
Acute ulcerogenic activity
Acute ulcerogenic activity was performed according to the method of Cioli
et al.4. The rats were divided into twelve groups consisting of six animals in
each group. Group I was kept as control, and received only vehicle (suspension
of 1% methyl cellulose). The activity was evaluated after oral administration
of test compounds or indomethacin at the dose of 60 mg/kg. The food was
withdrawn on the day before the experiment, but free access to water was
allowed. The animals were fed normal diet for 17 h after the drug treatment
and then sacrificed. The stomach was removed and opened along the greater
curvature, washed with distilled water and cleaned gently by dipping in saline.
The gastric mucosa was examined for damage by means of a magnifying glass.
The severity of mucosal damage for each stomach was assessed according to
the following scoring system-
N1-[4-(5-Methyl-3-isoxazolylsulfamoyl)phenyl]-4-(4-methoxylphenyl)-
4-oxobutanamide (9): Yield: 63 %; m.p. 176-178 °C; 1H-NMR (DMSO-d ,
δ, ppm): 2.03 (s, 3H, -CH , methoxazole), 2.58 (s, 3H, -OCH3), 2.83 & 3.367
(t, each, 2x -CH -), 6.15 3(s, 1H, methoxazole ring), 7.27 & 7.87 (d, each,
A2B2, 4H, p-subst2ituted phenyl ring), 7.48 & 7.75 (d, each, A2B2, 4H, p-anisole
ring), 9.60 (s,1H,-CONH-); MS (m/z): 443 (M+), 425, 379, 237, 131, 77; Anal.
C H N3O6S, calcd. C, 56.88; H, 4.77; N, 9.48; found C, 56.67; H, 4.82; N,
9.2511.21
N1-[4-(5-Methyl-3-isoxazolylsulfamoyl)phenyl]-4-(4-methylphenyl)-4-
1
oxobutanamide (10): Yield: 65 %; m.p. 186-188 °C; H-NMR (DMSO-d6, δ,
ppm): 2.33(s, 3H, -CH3, methoxazole), 2.45(s, 3H, -CH3), 2.82 & 3.37 (t each,
2x -CH2-), 6.17 (s, 1H, methoxazole ring), 7.72 & 8.1 (d, each, A2B , 4H,
p-substituted phenyl ring), 7.76 & 7.81 (d, each, A2B2, 4H, p-toluene 2ring),
9.36 (s, 1H, -CONH-): MS (m/z): 427 (M+), 409, 345, 175, 119, 91; Anal.
C H N3O5S, calcd. C, 59.01; H, 4.95; N, 9.83; found C, 58.85; H, 5.03; N,
9.2718.21
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 considered as severity index of gastric mucosal damage.
Antibacterial activity
All the newly synthesized compounds were screened for their antibacterial
activity against Staphylococcus aureus (ATCC-29737), Escherichia coli
(ATCC-8739) and Pseudomonas aeruginosa (NCLM-2035) at a concentration
of 100 mg/ml12. Compounds inhibiting growth of one or more of the above
microorganisms were further tested for minimum inhibitory concentration
(MIC). Solvent (DMF) and growth controls were kept. Minimum inhibitory
concentrations (MICs) were determined by broth dilution technique. The
nutrient broth, which contained logarithmic serially two fold diluted amount of
test compound and controls were inoculated with approximately 5x105 c.f.u. of
actively dividing bacteria cells. The cultures were incubated for 24 h at 37°C and
the growth was monitored visually and spectrophotometrically. Ciprofloxacin
was used as standard drug for comparison. The lowest concentration (highest
dilution) required to arrest the growth of bacteria was regarded as MIC.
N1-(4-{4-[3-(4-Methylphenyl)-3-oxopropylcarboxamido]phenylsulfonyl}
phenyl)-4-(4-methyl phenyl)-4-oxobutanamide (11): Yield: 70 %; m.p. 206-208
°C; 1H-NMR (DMSO-d , δ, ppm): 2.41 (s, 6H, 2x -CH3) 2.89 & 3.34 (t, each,
2x -CH -CH2-), 7.52 &67.87 (d, each, 2x A2B2, 8H, 2x p-toluene ring), 7.68
& 7.94 2(d, each, 2x A2B2, 8H, 2x p-substituted phenyl ring), 9.59 (s, 2H, 2x
-CONH-); MS: m/z 596 (M+), 360, 175, 119, 91, 77; Anal. C34H32N2O6S, calcd.
C, 68.44; H, 5.41; N, 4.69; found C, 68.51; H, 5.36; N, 4.64.
N1-(4-{4-[3-(4-Chlorophenyl)-3-oxopropylcarboxamido]phenylsulfonyl}
phenyl)-4-(4-chloro phenyl)-4-oxobutanamide (12): Yield: 57 %; m.p. 196 °C;
1H-NMR (DMSO-d6, δ, ppm): 2.84 & 3.36 (t, each, 2x -CH2-CH2-), 7.66 &
7.87 (d, each, 2x A2B2, 8H, 2x p-chlorobenzene ring), 7.71 & 8.16 (d, each, 2x
A2B2, 8H, 2x p-substituted phenyl ring), 9.74 (s, 2H, 2x -CONH-); MS: m/z 637
(M+), 473, 195, 139, 105, 77; Anal. C H26Cl2N2O6S, calcd. C, 60.29; H, 4.11;
N, 4.39; found C, 60.43; H, 4.15; N, 43.22 6.
RESULTS AND DISCUSSION
N1-(4-{4-[3-(2-Methoxyphenyl)-3-oxopropylcarboxamido]
phenylsulfonyl}phenyl)-4-(4-methoxy phenyl)-4-oxobutanamide (13): Yield:
55 %; m.p. 166 °C; 1H-NMR (DMSO-d6, δ, ppm): 2.56 (s, 3H, -OCH ), 2.89 &
3.36 (t, each, 2x -CH -CH2-), 7.68 & 7.95 (d, each, 2x A2B , 8H, 2x3p-anisole
ring), 7.75 & 8.15 (d2, each, 2x A2B2, 8H, 2x p-substituted2phenyl ring), 9.60
(s, 2H, 2x -CONH-); MS (m/z): 628 (M+ not observed), 135, 107, 77; Anal.
C H N2O8S, calcd. C, 64.96; H, 5.13; N, 4.46; found C, 64.88; H, 5.19; N,
4.3442.32
Chemistry
N1-(4-{4-[3-(4Ethylphenyl)-3-oxopropylcarboxamido]phenylsulfonyl}
phenyl)-4-(4-ethylphenyl)-4-oxobutanamide (14): Yield: 72 %; m.p. 166
1
°C; H-NMR (DMSO-d , δ, ppm): 1.27 (t, 6H, 2x CH3CH -), 2.58 (q, 4H,
2x CH3CH -), 2.82 & 3.638 (t, each, 2x -CH2-CH2-), 7.28 &27.93 (d, each, 2x
A2B2, 8H, 22x p-ethylbenzene ring), 7.76 & 8.13 (d, each, 2x A2B2, 8H, 2x
p-substituted phenyl ring), 10.03 (s, 2H, 2x -CONH-); MS: m/z 624 (M+), 189,
133, 105, 91, 77; Anal. C36H36N2O6S, calcd. C, 69.21; H, 5.81; N, 4.48; found
C, 69.35; H, 5.87; N, 4.33.
Biological evaluation
Antiinflammatory and ulcerogenic activities were performed on Wistar
rats of either sex, weighing 180-200 g. The animals were housed and treated
in accordance with the guidelines of Institutional Animal Ethics Committee
(IAEC). The animals were housed in groups of six (Animal house, Hamdard
University, New Delhi, India) and acclimatized to room conditions for at least
2 days before the experiments. The feeding was stopped the day before the
experiment, but they were allowed free access to water.
Antiinflammatory activity
The synthesized compounds were evaluated for their antiinflammatory
activity using carrageenan-induced rat paw edema method of Winter et al11.
The animals were randomly divided into groups of six. Group I was kept as
control, and received only 0.5% carboxymethyl cellulose (CMC) solution.
Groups II was kept as standard and received indomethacin (10 mg/kg p.o.).
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 minutes after the administration of the test compounds and
Titled compounds (5-14) were synthesized through one-pot reaction
method as depicted in Scheme 1. In the initial step, 3-aroylpropionic acids (1-
4) were prepared by condensing substituted benzenes with succinic anhydride
following Friedel-Craft’s acylation reaction conditions. The desired amides (5-
14) were synthesized by reacting 3-aroylpropionic acids (1-4) with appropriate
75

J. Chil. Chem. Soc., 55, Nº 1 (2010)
sulphonamide moiety in dry pyridine in presence of phosphorous oxychloride
(POCl ) as condensing agent and obtained in appreciable yields (54-72%). The
purity 3of the compounds was controlled by TLC in solvent system toluene:ethyl
acetate:formic acid (5:4:1, v/v/v). Spectral data and microanalysis data were in
agreement with the proposed structures.
The fragment-1/2 and the fragment R’’-SO -Ph+, could be important for
diagnosis of successful formation of the produ2ct, found correspondent to their
parent 3-aroylpropionic acid moiety and sulphonamide moiety, respectively.
Fragment-1/2 further splitted toAr-CºO+ and toAr+ and then to C H5+ (m/z=77).
In some cases, there was loss of 18 / 64 / 82 mass units may be6due to loss of
H2O / SO / SO2 + H O molecule(s), respectively. The proposed fragmentation
pattern is2presented i2n Chart 1.
In the nuclear magnetic resonance spectra (1H NMR; d ppm) showed two
triplets at around δ 2.55 & 3.53 (-CH2-CH2-); signals in the region δ 6.5-7.9
(aryl protons).
Biological evaluation
Antiinflammatory activity
The in-vivo antiinflammatory activity of the synthesized compounds
5-14 was evaluated at 10 mg/kg oral dose and compared with the standard
drug indomethacin at the same oral dose. The obtained results revealed that
two compounds, 6 and 9 which showed 54.56% and 51.81% inhibition,
respectively, were good in their antiinflammatory action and their activity was
comparable to that of the standard drug indomethacin (66.24%) at the same
dose level. Another compound, compound 10 showed significant activity with
47.13% inhibition (Table 1).
Results indicate that compounds having chlorobenzoyl propanoic acid
and/or sulfamethoxazole moiety as promoiety have high degree of activity.
Acute Ulcerogenesis
The synthesized amides were screened for their ulcerogenic activity in
albino rats after oral administration of test compounds or indomethacin at the
dose of 60 mg/kg. The tested compounds showed low ulcerogenic activity
ranging from 0.42 to 1.33, whereas the standard drug indomethacin showed
high severity index, 2.25 (Table 1). All the tested compounds exhibited better
gastro-intestinal profile as compared to the standard drug indomethacin.
Antibacterial activity
The compounds 5-14 were evaluated for their antibacterial activity
against S. aureus, E. coli and P. aeruginosa at a concentration of 100 mg/mL.
Broth dilution technique was followed for determining minimum inhibitory
concentration (MIC) of the compounds12. Ciprofloxacin was used as standard
drug for comparison, which showed MIC-6.25 mg/mL against all the three
bacterial strains. The compounds 7 showed very good activity against S. aureus
and E. coli with MIC 12.5 μg/mL. Similar type of activity was shown by the
compounds 5 against S. aureus and P. aurogenosa at 12.5 μg/mL concentration.
Compounds 5 and 8 showed significant activity against E. coli with MIC 25.0
μg/mL. Compounds 7 was good in its action against P. aurogenosa with
MIC 25.0 μg/mL. Other compounds were moderate in their action. From
the antibacterial results, it was observed that the compound derived from
chlorobenzoyl propionic acid were active among the tested compounds (Table
1).
The mass spectra showed molecular ion peaks in reasonable intensities
supporting the structure. The following points could be made regarding the
mass fragmentation pattern of compounds 5-l4: There was splitting of Ar-
COCH2CH2-CON-bond resulting in formation of Ar-COCH2CH2-CºO+
(fragment-1) or [Ar-COCH2CH=C=O]+ (fragment-2) and/or R’’-SO2-Ph+.
Table 1. Biological activity data of the title compounds.
Ulcerogenic
activity
Antiinflammatory activity
Antibacterial activity
(Minimum Inhibitory Concentration)
(% inhibition ± S.E.M.)a
Compound
(severity index ±
S.E.M.)a
After 2 hr
-
After 3 hr
-
S. aureus
E. coli
P. aurogenosa
Control
0.00
-
-
-
Indomethacin
52.01±4.27
66.24± 2.1
2.25±0.21
Ciprofloxacin
6.25
12.5
50
6.25
25
6.25
12.5
>100
25
5
6
21.02±2.56**
47.13±4.06
34.82±1.59**
54.56±2.10**
27.60±1.96**
18.89±1.70**
51.81±1.84**
47.13±2.96**
40.76±1.79**
31.00±2.45**
43.52±3.06**
11.68±1.12**
0.75±0.28**
1.00±0.29**
0.67±0.21**
0.58±0.20**
1.33.±0.33*
0.75±0.11**
0.83±0.21**
0.42±0.15**
0.83±0.17**
0.58±0.15**
50
7
24.42±1.69**
14.23±1.53**
40.97±2.22*
21.23±1.96**
35.03±3.40**
16.14±1.87**
32.06±2.49**
10.40±2.05**
12.5
50
12.5
25
8
50
9
>100
>100
>100
50
>100
>100
>100
>100
>100
>100
>100
>100
>100
50
10
11
12
13
14
50
>100
>100
>100
aRelative to the standard (Indomethacin) and data were analyzed by one-way ANOVA followed by Dunnett’s multiple comparison test for n=6 ; **P < 0.01;
*P < 0.05.
76

J. Chil. Chem. Soc., 55, Nº 1 (2010)
3.- B. Testa, P. Jenner Drug Metabolism, Chemical and biochemical aspect,
Marcel Dekker Inc, New York, 1976.
CONCLUSIONS
4.- V. Cioli, S. Putzolu, V. Rossi, P. S. Barcellona, C. Corradino, Toxicol. Appl.
Pharmacol. 50, 283, (1979).
5.- P. Selvam, D. F. Smee, B. B. Gowen, C. W. Day, D. L. Barnard, J. D.
Morrey, Antiviral Research 74, 81, (2007).
6.- H. S. Patel, H. J. Mistry, Phosphorus, Sulfur, and Silicon and the Related
Elements 179, 1085, (2004).
7.- E. H. Northey The Sulphonamides and allied compounds, American
Chemical Society Monograph Series, Reinhold, New York, 1948.
8.- M.Adamiec,J.Adamus,I.Ciebiada,A.Denys,J.Gebicki,Pharmacological
Reports 58, 246, (2006).
As concluding remarks we obtained herein two new compounds (6 & 9)
with antiinflammatory activity comparable to that of indomethacin (standard
drug), at the same dose level (10 mg/kg). Additionally, these derivatives were
very low in their ulcerogenic action, which is the main side effect of commonly
used NSAIDs. Compound 5 and 7 showed significant antibacterial activity
against the tested microbes with MIC-12.5 mg/mL. These results confirmed
the importance of exploring old drugs as safer templates to built new drug
candidates.
Acknowledgements: Financial support provided by Department of Science
& Technology, New Delhi (SERC-fast track proposal for young scientists), is
gratefully acknowledged. We are also thankful to the In-charge, animal house,
for providing animals for biological studies and Prof. P.K. Pillai for helping in
performing antibacterial activity of the compounds.
9.- M. S. Y. Khan, A. Husain, S. M. Hasan, M. Akhter, Scientia Pharmaceutica
70, 277, (2002).
10.- A. Husain, M. S. Y. Khan, Proceed. 19th American Peptide Symposium,
San Diego, California, USA, 2005; 567.
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