Synthesis and biological evaluation of benzothiazole derivatives of pyrimidines, acrylonitriles, and coumarins

Article abstract of DOI:10.3987/COM-05-10609

A number of benzothiazole derivatives of 2-aminopyrimidines (3a-b, 5, 6a-b, and 7), benzothiazole-3-arylacrylonitriles (10a-c), and benzothiazol-2-yl-coumarins (18a c, and 20) were synthesized by reacting benzothiazole derivatives with dicarbonyl compound

Full text of DOI:10.3987/COM-05-10609

HETEROCYCLES, Vol. 68, No. 2, 2006
347
HETEROCYCLES, Vol. 68, No. 2, 2006, pp. 347 – 355. © The Japan Institute of Heterocyclic Chemistry
Received, 31st October, 2005, Accepted, 22nd December, 2005, Published online, 27th December, 2005. COM-05-10609
SYNTHESIS
AND
BIOLOGICAL
EVALUATION
OF
BENZOTHIAZOLE
DERIVATIVES
OF PYRIMIDINES,
┼
ACRYLONITRILES, AND COUMARINS
Amal M. Youssef, Hany M. Mohamed, Caitlin Czezowski, Athar Ata, and Alaa
S. Abd-El-Aziz*
Department of Chemistry, The University of Winnipeg, Winnipeg, Manitoba,
R3B 2E9, Canada
E-mail: a.abdelaziz@uwinnipeg.ca
Abstract- A number of benzothiazole derivatives of 2-aminopyrimidines (3a-b,
5
, 6a-b, and 7), benzothiazole-3-arylacrylonitriles (10a-c), and benzothiazol-2-
yl-coumarins (18a c, and 20) were synthesized by reacting benzothiazole
derivatives with dicarbonyl compounds, and aromatic aldehydes. The
unexpected 2-(4-methoxyphenyl)benzo[d]thiazole (14) was obtained as a unique
product via the reaction of 2-aminothiophenol with ethyl 3-(4-methoxyphenyl)-
2
-scyanoacrylate.
2-(Benzo[d]thiazol-2-yl)-3-(4-hydroxyphenyl)acrylonitrile
(
10a) exhibited activity against Staphylococcus aureus. 2-(Benzo[d]thiazol-2-
ylamino)pyrimidine-4,6-(1H,5H)-dione (3b) showed antibacterial activity
selectivity against Corynebacterium xerosis. 2-(Benzo[d]thiazol-2-ylamino)-6-
methylpyrimidin-4(3H)-one (5) showed weak anti-fungal activity against
Candida albicans.
INTRODUCTION
The benzothiazole nucleus is found in various marine or terrestrial natural compounds, which have
1
-4
interesting biological activities. The compounds having benzothiozole moiety are reported to exhibit
5
,6
7
8
9
different bioactivities including antitumor,
activities.
antimicrobial, anti-mycobacterial, and antimalarial
It has also been reported in the literature that 2- and 5-substituted benzothiazoles and its bioisosteres;
benzoxazole and benzimidazole derivatives had antimicrobial activities against some Gram-positive,
Gram-negative bacteria and the yeast Candida albicans, and these compounds provided a wide variety of
in vitro antimicrobial effects especially against the enterobacter Pseudomonas aeruginosa and the yeast
1
0-20
Candida albicans.
┼
A part of the work was presented at the Canadian Society of Chemistry Conference, Saskatoon in May 2005.

348
HETEROCYCLES, Vol. 68, No. 2, 2006
2
1
22
23
Pyrimidines, acrylonitriles, and coumarins have also shown potent antimicrobial activities. In our
2
4
continuing effort to synthesize bioactive compounds, we have synthesized some novel benzothiazole
derivatives of pyrimidines, acrylonitriles and coumarins and evaluated their antimicrobial activities.
RESULTS AND DISSCUSSION
2
5
Reacting the guanidinobenzothiazole derivative (1) with diethyl malonate (2a) or diethyl ethylmalonate
2b) in bromobenzene yielded the corresponding 2-(benzo[d]thiazol-2-ylamino)pyrimidine-4,6-(1H,5H)-
(
dione (3a) and 2-(benzo[d]thiazol-2-ylamino)-5-ethylpyrimidine-4,6-(1H,5H)-dione (3b), respectively.
Analogously, heating 1 with ethyl acteoacetate (4) in methanol in the presence of sodium methoxide
resulted in the formation of 2-(benzo[d]thiazol-2-ylamino)-6-methylpyrimidin-4(3H)-one (5) (Scheme 1).
Compounds (3a, 3b and 5) were isolated as stable white solids and spectroscopic methods were used to
1
determine their structures. The H NMR spectra of compounds (3a, 3b and 5) showed characteristic
1
signals for the protons at position 5 as a singlet at δ 5.05, 3.25 and 5.34 respectively. The H NMR
spectrum of compound (3b) showed two signals as a quartet at δ 2.32 and a triplet at δ 1.05 due to the
ethyl group. The amide protons resonated at δ 11.62-11.31, while the amine bridge-head protons appeared
at δ 7.44-7.32 for these compounds.
N
S
O
N
S
NH
NH
EtO
EtO
+
NH
N
R
H N
HN
O
2
1
O
2
POCl3
O
Me
O
a,b
R
a; R = H
b; R = Et
MeOH
MeONa
3
OEt
N
S
O
4
NH
N
N
Cl
H
H
N
N
N
N
N
N
Me
Me
Cl
a,b
R
POCl3
S
S
N
HN
6
5
7
Cl
O
a; R = H
b; R =Et
Scheme 1
Reaction of compounds (3a, 3b and 5) with phosphorous oxychloride resulted in the formation of
1
chloropyrimidine derivatives (6a,b and 7) (Scheme 1). The H NMR spectra of 6a, 6b and 7 exhibited
downfield signals for H-5 and ethyl group in shifted at δ 7.46, 7.45, 2.60 and 1.30, respectively. These
observations suggested the aromatization of the pyrimidine ring and the presence of the neighboring
chlorine atoms as well.
26
27
As previously reported, reaction of o-aminothiophenol (8) with α-cyanocinnamonitrile (9a-c) under
acidic conditions was carried out to produce 2-(benzo[d]thiazol-2-yl)-3-arylacrylonitriles (10a,b and

HETEROCYCLES, Vol. 68, No. 2, 2006
349
2
6
28
1
0c ) (Scheme 2). Under these reaction condition, ethyl 3-(4-methoxyphenyl)-2-cyanoacrylate (11)
afforded 2-(4-methoxyphenyl)benzo[d]-thiazole (14) as a unique product. This product was unexpectedly
formed as we were expecting to get ethyl 2-(benzo[d]thiazole-2-yl)-3-(4-methoxyphenyl)acrylate (12) as
a product in this reaction. The formation of compound (14) might be due to the nucleophilic addition of
the thiol group to the acrylate β-carbon to give an acyclic intermediate (13), which underwent cyclization
2
9
and elimination of ethyl cyanoacetate (Scheme 3). The role of acetic acid in the formation of compound
(
14) was not clearly understood.
1
Structures of 10a,b were confirmed with the aid of spectroscopic data. The H NMR spectra showed the
characteristic signals for olefinic protons at δ 8.26-8.18 as singlets. The formation of compound (14) was
1
evident from the H NMR spectrum, which did not show the resonances for olefinic and carboxylic ester
protons. The MS of 14 also confirmed its structure, which exhibited molecular ion peak at m/z 241 as a
base peak.
R1
R
R
R1
NH2
SH
CN
CN
+H/ EtOH
N
+
CN
H
S
8
9a-c
1
0a-c
a; R = OH
b; R = OH, R =OMe
1
c; R = OMe
Scheme 2
MeO
N
+H/ EtOH
CO Et
2
S
12
MeO
NH2
S
NH2
SH
+H/ EtOH
CN
CO Et
N
S
CN
OMe
+
H
CO
Et
2
2
8
11
14
MeO
13
Scheme 3

350
HETEROCYCLES, Vol. 68, No. 2, 2006
Synthesis of 3-(benzo[d]thiazol-2-yl)coumarins via Knoevenagel condensation of 2-(benzo[d]thiazol-2-
yl)acetonitrile with 2-hydroxybenzaldehydes and subsequent acid hydrolysis of iminocoumarins has been
3
0,31
reported.
In this study a new procedure was developed one-step reaction for the synthesis of these
3
2
compounds. This was accomplished by the reaction of ethyl 2-(benzo[d]thiazole-2-yl)acetate (15) and
the appropriate aromatic aldehydes (16a-c, or 17) under the basic condition at room temperature for 1 h
3
0
31
33
to give the corresponding 3-(benzo[d]thiazol-2-yl)coumarin derivatives (18a, b, c, and 19 ) (Scheme
1
4
9
). The H NMR data indicated the formation of the coumarin ring hence, the low-field resonances at δ
.05-9.79 was due to the C-4 proton of the coumarin system along with signals for the protons of the
benzthiazole fragment.
R3
R2
CHO
OH
N
O
R3
R2
S
R1
O
R1
1
6a-c
18a-c
a;R =R =R = H
1
2
3
b;R =R = I, R = H
1
3
2
N
S
COOEt
CH2
c;R1=R2 = H, R3 = Cl
15
CHO
OH
N
S
O
1
7
O
19
Scheme 4
Antimicrobial activity of all synthesized compounds was assayed against various pathogenic bacteria and
Candida albicans by using disk agar diffusion method. 2-(Benzo[d]thiazol-2-ylamino)pyrimidine-4,6-
(
1H,5H)-dione (3b) and 2-(benzo[d]thiazol-2-yl)-3-(4-hydroxyphenyl)acrylonitrile (10a) exhibited
moderate antibacterial activity against Staphylococcus aureus and Corynebacterium xerosis, respectively.
The minimal inhibitory concentrations of compounds (3b and 10) were found to be 35 and 40 μg/mL,
respectively. 2-(Benzo[d]thiazol-2-ylamino)-6-methylpyrimidin-4(3H)-one (5) showed weak anti-fungal
activity against Candida albicans.
EXPERIMENTAL
1
Melting points were measured in open capillary tubes and are uncorrected. H NMR spectra were
6
recorded at 300 MHz on a Bruker DPX 300 spectrometer, in DMSO-d , with chemical shifts being

HETEROCYCLES, Vol. 68, No. 2, 2006
351
1
calculated from the solvent signals. NH, NH
2
and OH groups were confirmed doing D
2
O exchange H
NMR spectroscopy.13C NMR spectra were also recorded on the same instrument at 75 MHz. MS spectra
were reported on Hewlett Packard 5989 B Mass Spectrometer. IR spectra were recorded on Bomem MB-
Series FT-IR spectrophotometer by using KBr pellet.
2
-(Benzo[d]thiazol-2-ylamino)-5-substituted pyrimidine-4,6-(1H,5H)-diones (3a-b)
A solution of 1 (1.92 g, 10 mmol) and the appropriate substituted diethyl malonate (10 mmol) in
bromobenzene (20 mL) was refluxed for 4 h. After cooling it to rt, the separated solid product was filtered,
washed with ethanol and dried.
o
1
3
a was white solid from DMF-ethanol; mp >260 C; yield 80 %; H NMR δ 11.62 (br, NH amide, 1H),
7
.82 (d, benzothiazole, J = 8.8 Hz, 1H), 7.40 (d, benzothiazole, J = 7.2 Hz, 1H), 7.32 (s, NH, 1H), 7.22 (t,
-
1
benzothiazole, J = 8.8 Hz, 1H), 7.12 (t, benzothiazole, J = 7.2 Hz, 1H), 5.05 (s, H-5, 2H); IR cm (KBr)
3
3
3
7
436 ( amide NH) 3026 (bridge-head NH), 1650, 1608 (C=O); Anal. Calcd for C11
.10; N, 21.53; S, 12.32. Found: C, 51.16; H, 3.11; N, 21.28.
8 4 2
H N O S: C, 50.76; H,
o
1
b was a white solid from ethanol; mp 258-260 C; yield 83 %; H NMR δ 11.31 (br, NH amide, 1H),
.78 (d, benzothiazole, J = 8.8 Hz, 1H), 7.66 (d, benzothiazole, J = 7.2 Hz, 1H), 7.44 (br s, NH, 1H), 7.36
2
(t, benzothiazole, J = 8.8 Hz, 1H), 7.10 (t, benzothiazole, J = 7.2 Hz, 1H), 3.25 (s, H-5, 1H), 2.32 (q, CH ,
-
1
J = 3.2 Hz, 2H), 1.05 (t, CH
3
, J = 3.2 Hz, 3H); IR cm (KBr) 3333 (amide NH) 3063 (bridge-head NH),
S: C, 54.15; H, 4.19; N, 19.43; S, 11.12. Found: C, 54.47;
1
710, 1663 (C=O); Anal. Calcd for C13
H, 4.30; N, 19.23.
-(Benzo[d]thiazol-2-ylamino)-6-methylpyrimidin-4(3H)-one (5)
12 4 2
H N O
2
To a mixture of 1 (1.92 g, 10 mmol) and methanol (5 mL); a solution of ethyl acetoacetate (4) (1.30 g, 10
mmol) in sodium methoxide and methanol (10 mL) was added. The reaction mixture was heated while
stirring for 1 h until complete precipitation. The white solid product was collected by filtration, dried and
o
1
recrystallized from DMF-ethanol mp >260 C; yield 85 %; H NMR δ 10.90 (br, NH amide, 1H), 7.70 (d,
benzothiazole, J = 8.8 Hz, 1H), 7.40 (d, benzothiazole, J = 7.2 Hz, 1H), 7.23 (t, benzothiazole, J = 8.8 Hz,
-1
1
H), 7.11 (t, benzothiazole, J = 7.2 Hz, 1H), 5.34 (s, H-5, 1H); 2.45 (s, CH , 3H); IR cm (KBr) 3386
3
(
amide NH), 3263 (bridge-head NH), 1686 (C=O); Anal. Calcd for C12H N OS: C, 55.80; H, 3.90; N,
10 4
2
1.69; S, 12.41. Found: C, 55.43; H, 3.95; N, 21.72.
General procedure for the synthesis of 6a, b and 7
Compounds (3a, b and 5) (10 mmol) were heated under reflux for 4 h with excess of phosphorous
oxychloride (20 mL). The reaction mixture was then decanted portion wise on ice. The solid formed was
filtered, washed with water and ether and then dried under reduced pressure.
N-(4,6-Dichloropyrimidin-2-yl)benzo[d]thiazol-2-amine (6a)
o
1
Yellow solid from DMF-ethanol mp >260 C; yield 80 %; H NMR δ 7.99 (d, benzothiazole, J = 8.8 Hz,
H), 7.70 (d, benzothiazole, J = 7.2 Hz, 1H), 7.45 (s, H-5, 1H), 7.43 (t, benzothiazole, J = 8.8 Hz, 1H),
1

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HETEROCYCLES, Vol. 68, No. 2, 2006
-
1
+
7
2
1
.25 (t, benzothiazole, J = 7.2 Hz, 1H); IR cm (KBr) 3051 (bridge-head NH); MS m/z (%): 297 (M , 66),
+
96 (M -1, 100), 261 (88), 225 (17); Anal. Calcd for C11
H
6
N
4
Cl
2
S: C, 44.46; H, 2.04; Cl, 23.86; N,
8.85; S, 10.79. Found: C, 44.43; H, 2.19; N, 18.55.
N-(4,6-Dichloro-5-ethylpyrimidin-2-yl)benzo[d]thiazol-2-amine (6b)
o
1
White solid from DMF-ethanol mp >260 C; yield 83 %; H NMR (300 MHz) δ 8.0 (d, benzothiazole, J =
8
.8 Hz, 1H), 7.71 (d, benzothiazole, J = 7.2 Hz, 1H), 7.43 (t, benzothiazole, J = 8.8 Hz, 1H), 7.25 (t,
-1
benzothiazole, J = 7.2 Hz, 1H), 2.60 (q, CH , J = 3.5 Hz, 2H), 1.30 (t, CH , J = 3.5 Hz, 3H); IR cm
2
3
(
10 4 2
KBr) 3057 (bridge-head NH); Anal. Calcd for C13H N Cl S: C, 48.01; H, 3.10; Cl, 21.80; N, 17.23; S,
9.86. Found C, 48.39; H, 3.00; N, 17.48.
N-(4-Chloro-6-methylpyrimidin-2-yl)benzo[d]thiazol-2-amine (7)
o
1
Off white solid from DMF-ethanol mp >260 C; yield 85 %; H NMR δ 8.00 (d, benzothiazole, J = 8.8 Hz,
1H), 7.71 (d, benzothiazole, J = 7.2 Hz, 1H), 7.46 (s, H-5, 1H), 7.40 (t, benzothiazole, J = 8.8 Hz, 1H),
-1
7.25 (t, benzothiazole, J = 7.2 Hz, 1H), 2.50 (s, CH
3
, 3H); IR cm (KBr) 3160 (bridge-head NH); Anal.
9 4
Calcd for C12H N
ClS: C, 52.08; H, 3.28; Cl, 12.81; N, 20.24; S, 11.59. Found: C, 51.76; H, 3.40; N,
1
9.99.
-(Benzo[d]thiazol-2-yl)-3-arylacrylonitrile (10a-c)
2
To a mixture of α-cyanocinnamonitrile derivatives (9a-c) (10 mmol) and 2-aminobenzenethiol (8) (1.25
g, 10 mmol) in ethanol (10 mL), acetic acid (0.63 g, 10 mmol) was added. The mixture was refluxed for 3
h, and then allowed to stand overnight. The resultant yellow precipitate is isolated by suction and
recrystallized from a suitable solvent. Yield 84-87 %.
o
1
1
0a yellow crystals from ethanol-water; mp 218-220 C; H NMR δ 10.67 (br, OH, 1H), 8.18 (s, =CH,
1
H), 8.07 (d, benzothiazole, J = 8.8 Hz, 1H), 7.98 (d, benzothiazole, J = 7.2 Hz, 1H), 7.90 (d, aromatic, J
=
8.1 Hz, 1H), 7.51 (t, benzothiazole, J = 8.8 Hz, 1H), 7.43 (t, benzothiazole, J = 7.2 Hz, 1H), 6.94 (d,
-1
aromatic, J = 8.1 Hz, 2H); IR cm (KBr) 3347 (OH), 2214 (CN); Anal. Calcd for C16
10 2
H N OS: C, 69.04;
H, 3.62; N, 10.06; S, 11.52. Found: C, 68.65; H, 3.51; N, 10.36.
o
1
1
0b yellow crystals from chloroform ; mp 175-177 C; H NMR δ 10.38 (br, OH, 1H), 8.26 (s, =CH, 1H),
.14 (d, benzothiazole, J = 8.8 Hz, 1H), 8.03 (d, benzothiazole, J = 7.2 Hz, 1H), 7.83 (s, aromatic, 1H),
.65 (d, aromatic, J = 8.1 Hz, 1H), 7.56 (t, benzothiazole, J = 8.8 Hz, 1H), 7.49 (t, benzothiazole, J = 7.2
8
7
-
1
3
Hz, 1H), 6.94 (d, aromatic, J = 8.1 Hz, 1H), 3.85 (s, OCH , 3H); IR cm (KBr) 3067 (OH), 2209 (CN);
Anal. Calcd for C17
-(4-Methoxyphenyl)benzo[d]thiazole (14)
A mixture of ethyl 3-(4-methoxyphenyl)-2-cyanoacrylate (11) (2.31 g, 10 mmol), 2-aminothiophenol (8)
1.25 g, 10 mmol) and few drops of acetic acid was refluxed in ethanol (10 mL) for 3 h. The solution was
cooled to rt and allowed to stand overnight. The solid precipitate was collected by filtration and
12 2 2
H N O S: C, 66.22; H, 3.92; N, 9.08; S, 10.40. Found: C, 65.83; H, 3.82; N, 9.29.
2
(
o
1
recrystallized from ethanol; mp 115-117 C; yield 95 % (2.289 g); H NMR δ 8.13 (d, benzothiazole, J =

HETEROCYCLES, Vol. 68, No. 2, 2006
353
8
.8 Hz, 1H), 8.07 (d, aromatic, J = 8.1 Hz, 2H), 8.02 (d, benzothiazole, J = 7.2 Hz, 1H), 7.56 (t,
benzothiazole, J = 8.8 Hz, 1H), 7.43 (t, benzothiazole, J = 7.2 Hz, 1H), 7.11 (d, aromatic, J = 8.1 Hz, 2H),
-1
+
3
.87 (s, OCH , 3H); IR cm (KBr) 1605 (C=N); MS m/z (%): 241 (M , 100), 226 (42), 198 (34), 154 (12),
3
1
21 (6), 108 (5), 69 (13), 45 (9); Anal. Calcd for C14H11NOS: C, 69.68; H, 4.59; N, 5.80; S, 13.29. Found:
C, 70.02; H, 4.68; N, 6.05.
-Benzo[d]thiazol-2-yl)coumarin derivatives (18a-c and 19)
3
A mixture of ethyl 2-(benzo[d]thiazol-2-yl)acetate (15) (1.11 g, 5 mmol), the appropriate aromatic
aldehyde (5 mmol) and few drops of piperidine in ethanol (10 mL) was stirred at rt where an immediate
precipitation occurs. The stirring was continued for 30 min. until complete precipitation. The solid
formed was filtered, dried and recrystallized from the appropriate solvent.
3
-(Benzo[d]thiazol-2-yl)coumarin (18a)
o
1
White crystals from ethanol mp 215 C; yield 98 %; H NMR δ 9.05 (s, H-4, 1H), 8.13 (d, benzothiazole,
J= 8.8 Hz, 1H), 8.01 (m, benzothiazole and aromatic, 2H), 7.59 (t, benzothiazole, J = 8.8 Hz, 1H), 7.49
-1
(
m, benzothiazole and aromatic, 4H); IR cm (KBr) 1717 (C=O).
3
-(Benzo[d]thiazol-2-yl)-6,8-diiodocoumarin (18b)
o
1
White crystals from DMF-ethanol mp >260 C; yield 99 %; H NMR δ 9.05 (s, H-4, 1H), 8.42 (s,
aromatic, 1H), 8.36 (s, aromatic ,1H), 8.13 (d, benzothiazole, J= 8.8 Hz, 1H), 8.04 (d, benzothiazole, J=
-1
7.2 Hz, 1H), 7.53 (t, benzothiazole, J = 8.8 Hz, 1H), 7.46 (t, benzothiazole, J = 7.2 Hz, 1H); IR cm
(
KBr) 1726 (C=O); Anal. Calcd for C16 NO S: C, 36.18; H, 1.33; I, 47.79; N, 2.64; S, 6.04. Found: C,
H
7
2 2
I
3
3
5.79.; H, 1.24; N, 2.87.
-(Benzo[d]thiazol-2-yl)-6-chlorocoumarin (18c)
o
1
White crystals from DMF-ethanol mp 239-241 C; yield 97 %; H NMR δ 9.01 (s, H-4, 1H), 8.31 (s,
aromatic, 1H), 8.15 (d, benzothiazole, J= 8.8 Hz, 1H), 8.10 (d, aromatic, J = 8.1 Hz, 2H), 8.04 (d,
benzothiazole, J= 7.2 Hz, 1H), 7.53 (t, benzothiazole, J = 8.8 Hz, 1H), 7.45 (t, benzothiazole, J = 7.2 Hz,
-1
1
H), IR cm (KBr) 1728 (C=O).
3
-(Benzo[d]thiazol-2-yl)- 3H-benzo[f]coumarin (19)
o
1
White crystals from DMF mp >260 C; yield 98 %; H NMR δ 9.79 (s, H-4, 1H), 8.66 (d, aromatic, J =
8
.4 Hz, 1H), 8.31 (d, benzothiazole, J= 8.8 Hz, 1H), 8.17(m, benzothiazole and aromatic, 6H), 7.59 (t,
-1
benzothiazole, J = 8.8 Hz, 1H), 7.48 (t, benzothiazole, J = 7.2 Hz, 1H), IR cm (KBr) 1711 (C=O).
ANTIMICROBIAL EVALUATION
All of the synthesized compounds (3a, b, 5, 6a, b, 7, 10a-c, 14, 18a-c and 19) were tested for antibacterial
activity against Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Pseudomonas
aeruginosa, Staphylococcus agalactiae, Staphylococcus typhimu, Bacillus cereus, and
3
4
Corynebacterium xerosis at a dose of 25 μg/mL by using the agar disk diffusion assay.

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HETEROCYCLES, Vol. 68, No. 2, 2006
INHIBITION ZONE MEASURMENT
The method of choice for the antimicrobial assay was the Kirby-Bauer Disc method. The compounds to
be tested were dissolved in DMSO and 32-250 μL of each of these solutions was applied on serial paper
disks with a diameter of 7 mm. These disks were allowed to dry and then placed on Mueller Hinton II
o
agar inoculated with the test organism. These plates were then incubated at 37 C for 24 h and the
resulting inhibition zones were measured. A control without the test compound was included for each
organism.
MINIMAL INHIBITORY CONCENTRATION (MIC)
3
5
The MIC values were measured by using the standard broth dilution antimicrobial susceptibility test.
o
The test organism were grown in Mueller Hinton II agar for 24h at 37 C. The compounds to be tested
were dissolved in DMSO and two-fold serial dilutions were prepared. The tubes were then inoculated
o
with 100 μL of the 24h test organism culture and were incubated at 37 C for 24 h.
ACKNOWLEDGEMENTS:
The funding provided by Natural Sciences and Engineering Research Council, Canada (NSERC) to
support this work is gratefully acknowledged.
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