Microwave-assisted synthesis and antimicrobial activity of some imidazo[2,1-b][1,3,4]thiadiazole derivatives

Article abstract of DOI:10.1007/s00044-011-9671-8

A simple and efficient method was developed for the synthesis of 2,6-disubstituted-imidazo[2,1-b][1,3,4] thiadiazoles under microwave (MW) activation using 2-amino-5-substituted-1,3,4-thiadiazoles and appropriate bromo ketones as materials. All reactions

Full text of DOI:10.1007/s00044-011-9671-8

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res (2012) 21:1550–1556
DOI 10.1007/s00044-011-9671-8
ORIGINAL RESEARCH
Microwave-assisted synthesis and antimicrobial activity
of some imidazo[2,1-b][1,3,4]thiadiazole derivatives
•
Sharad Dhepe Sujeet Kumar R. Vinayakumar
•
•
•
Sureshbabu A. Ramareddy Subhas S. Karki
Received: 16 February 2011 / Accepted: 12 May 2011 / Published online: 27 May 2011
Ó Springer Science+Business Media, LLC 2011
Abstract A simple and efficient method was developed
for the synthesis of 2,6-disubstituted-imidazo[2,1-b][1,3,4]
thiadiazoles under microwave (MW) activation using
2-amino-5-substituted-1,3,4-thiadiazoles and appropriate
bromo ketones as materials. All reactions demonstrated the
benefits of MW reactions: convenient operation, short
reaction time, and good yields. All derivatives were char-
acterized by IR, NMR, and Mass spectroscopy. Antibac-
terial and antifungal activity was performed using cup plate
method against Staphylococcus aureus, Klebsiella, and
Candida albicans microorganisms. 2-(4-nitro benzyl)-6-(4-
bromo phenyl)imidazo[2,1-b][1,3,4]thiadiazole (4Ce) was
the only derivative which showed activity against Klebsi-
ella at low micromolar concentration (5 lg/ml) with
moderate zone of inhibition. And 2-(4-nitro benzyl)-6-
(4-fluoro phenyl)imidazo[2,1-b][1,3,4]thiadiazole (4Cf) as
the most potent antifungal active derivative at 50 lg/ml
against C. albicans on comparison to standard fluconazole.
pathogenic bacteria towards available antibiotics is rapidly
becoming a major world wide problem. In addition to that,
fungal infections continue to increase rapidly because of
the increased number of immunocompromised patients.
Levamisole, a well-known immunomodulator, (Amery
et al., 1984) the possibility of reducing harmful effects of
cytotoxic agents on immune system. Compounds closely
related to levamisole have been investigated. Andreani
et al. (1991a, b) reported that some imidazo[2,1-b]thiazole
are more active than levamisole. Many derivatives con-
taining the imidazo[2,1-b][1,3,4]thiadiazole ring system,
which is bioisosteric with the imidazo[2,1-b]thiazole
system of Levamisole, are being explored. Similarly, a large
number of imidazo[2,1-b][1,3,4]thiadiazole have been
reported to possess diverse pharmacological properties
such as anticancer (Gadad et al., 1999; Karki et al., 2011),
antitubercular (Gadad et al., 2004; Kolavi et al., 2006),
antibacterial (Gadad et al., 2000; Lamani et al., 2009),
antifungal (Andotra et al., 1997; Chen et al., 2007), anti-
convulsant, analgesic (Khazi et al., 1996), antisecretory
(Andreani et al., 2000), anti-inflammatory (Andreani et al.,
1982; Jadhav et al., 2008; Gadad et al., 2008), cardiotonic
(Andreani et al., 1986) diuretic (Andreani et al., 1987), and
herbicidal activities (Andreani et al., 1991a, b).
Keywords Microwave ꢀ
Imidazo[2,1-b][1,3,4]thiadiazole ꢀ Synthesis ꢀ
Antibacterial activity ꢀ Antifungal activity
Introduction
The microwave (MW) radiation region is located
between infrared radiation and radio waves. MWs have
wavelengths of 1 mm–1 m. It has been known for a long
time that MWs can be used for heating materials. In fact,
the development of MW ovens for the heating of food has
more than a 50-year history (Buffler, 1993).
The design of new compounds to lead with resistant bac-
teria has become one of the most important areas of anti-
bacterial research today, that is because of resistance of
MW technology has been used since the late 1970s, in
inorganic chemistry, while it has been implemented in
organic chemistry since the mid-1980s. The development
of the technology for organic chemistry has been rather
slow compared, to for example, combinatorial chemistry
S. Dhepe ꢀ S. Kumar ꢀ R. Vinayakumar ꢀ
S. A. Ramareddy ꢀ S. S. Karki (&)
Department of Pharmaceutical Chemistry, KLE University’s
College of Pharmacy, Bangalore 560 010, Karnataka, India
e-mail: subhasskarki@gmail.com
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Med Chem Res (2012) 21:1550–1556
1551
and computational chemistry. Since the mid-1990s, how-
ever the number of publications has increased significantly.
The main reason for this increase includes the availability
of commercial MW equipment intended for organic
chemistry and the development of the solvent-free tech-
nique, which has improved the safety aspects, but are
mostly due to an increased interest in shorter reaction
times.
filtered the precipitate, washed with water, and recrystal-
lized from ethanol.
2-Amino-5-benzyl-1,3,4-thiadiazole (3A)
MSm/z 192.00; FT IR (v cm-1)3021, 2936, 1520, 1465, 1350,
1300, 1172, 1095, 1010. 1H NMR (CDCl3, 400 MHz) d 4.14
(s, 2H, –CH2–), 7.12 (s, –NH2, 2H), 7.23–7.34 (m, 5H).
MW-assisted organic synthesis is suited to the increased
demand in industry because of short reaction times and
expanded reaction range. In particular, there is a require-
ment in the pharmaceutical industry for a higher number of
novel chemical entities to be produced.
2-Amino-5-(4-chlorobenzyl)-1,3,4-thiadiazole (3B)
MS m/z 226.10; FT IR (v cm-1) 3162, 3034, 2945, 2893,
1696, 1566, 1494, 1355, 1306, 1170, 1092, 1014. 1H NMR
(CDCl3, 400 MHz) d 4.30 (s, 2H. –CH2–), 7.06 (s, –NH2,
2H), 7.55 (d, J = 8 Hz, 2H), 8.20 (d, J = 8 Hz, 2H).
In general, most organic reactions have been heated using
traditional heat transfer equipment such as oil baths, sand
baths, and heating jackets. These heating techniques are,
however, rather slow, and a temperature gradient can
develop within the sample. In addition, local overheating can
lead to product, substrate, and reagent decomposition. In
contrast, in MW dielectric heating, the MW energy is
introduced into the chemical reactor remotely, and direct
access by the energy source to the reaction vessel is obtained.
The MW radiation passes through the walls of the vessel and
heats only the reactants and solvent, not the reaction vessel.
In view of the above and in continuation of our research on
fused imidazo[2,1-b][1,3,4]thiadiazoles, we report here
the MW and conventional-assisted synthesis, antibacterial,
and antifungal activity of some 2-(4-substituted benzyl)-6-
phenyl imidazo[2,1-b][1,3,4]thiadiazoles.
2-Amino-5-(4-nitrobenzyl)-1,3,4-thiadiazole (3C)
MS m/z 237.00; FT IR (v cm-1) 3168, 3120, 3034, 2853,
1
2738, 1691, 1571, 1517, 1351, 1177. H NMR (DMSO,
400 MHz) d 4.32 (s, 2H. –CH2–), 7.08 (s, –NH2, 2H), 7.56
(d, J = 8 Hz, 2H), 8.19 (d, J = 8 Hz, 2H).
Synthesis of imidazo[2,1-b][1,3,4]thiadiazoles (4)
Conventional method The appropriate 2-amino-1,3,4-
thiadiazole 3 (30 mmol) was treated with the appropriate
a-bromo ketone (30 mmol) in ethanol (150 ml). The mix-
ture was refluxed for 8–10 h. Excess of solvent was
removed under reduced pressure, and the solid hydrobro-
mide salt separated was filtered, washed with cold ethanol,
and dried. Neutralization of hydrobromide salts with cold
aqueous solution of sodium carbonate yielded the corre-
sponding free base which was filtered and which were
recrystallised with EtOH to yield products 40–60%.
Experimental
Chemistry
The melting points are uncorrected. Silica gel plates were
used for the TLC using CHCl3:MeOH. The IR spectra were
1
recorded in KBr on a Jasco 430?; the H NMR spectra
MW method
were recorded in CDCl3 on a Bruker (400 MHz), and
J values are reported in hertz (Hz). Mass spectra were
recorded in triple quadrapole LCMS-6410 from Agilent
technologies.
The appropriate 2-amino-1,3,4-thiadiazole 3 (0.01 M) trea-
ted with the appropriate bromo ketone (0.01 M) in DMF
(30 ml) was irradiated in a MW oven for 4–7 min at 640 W.
Completion of the reaction was monitored by TLC using
CHCl3 andCH3OH (9:1)aseluent. The resultingmixturewas
cooled to room temperature and neutralization of hydrobro-
mide salts with cold aqueous solution of sodium carbonate
yielded the corresponding free base in 75–84% yield.
General procedure for preparation of 3A–3C
The mixture of substituted/phenyl acetic acid (0.1 M) and
thiosemicarbazide (0.15 M) was added slowly to the round
bottom flask containing concentrated H2SO4 (30 ml) with
constant stirring in ice bath. After complete addition, ice
bath was replaced by water bath and slowly heated to
70–80°C and maintained at that temperature for 7 h. After
cooling to room temperature, the contents of reaction were
poured into ice water and made basic with ammonia,
2-Benzyl-6-(4-chlorophenyl)imidazo
[2,1-b][1,3,4]thiadiazole (4Aa)
MS m/z 324.10; FT IR (v cm-1) 3127, 3061, 3032, 2917,
2848, 1523, 1256, 1027. 1H NMR (CDCl3, 400 MHz) d 4.30
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Med Chem Res (2012) 21:1550–1556
(s, 2H, –CH2–), 7.32–7.39 (m, 7H), 7.74 (d, J = 8 Hz, 2H),
7.95 (s, 1H, im).
–CH2–), 7.22 (d, J = 8 Hz. 2H), 7.27 (d, J = 8 Hz, 2H),
7.36 (d, J = 8 Hz, 2H), 7.69 (d, J = 8 Hz, 2H), 7.92 (s, 1H,
im).
2-Benzyl-6-(4-methylphenyl)imidazo
[2,1-b][1,3,4]thiadiazole (4Ab)
2-(4-Chlorobenzyl)-6-(4-methoxyphenyl)imidazo
[2,1-b][1,3,4]thiadiazole (4Bc)
MS m/z 306.01; FT IR (v cm-1) 3134, 3058, 3033, 2973,
2864, 1524, 1470, 1232, 1177, 1092.1H NMR (CDCl3,
400 MHz) d 2.30 (s, 3H, CH3), 4.43 (s, 2H, –CH2–), 7.20
(d, J = 8 Hz, 2H), 7.29–7.41 (m, 5H), 7.73 (d, J = 8 Hz,
2H), 8.55 (s, 1H, im).
MS m/z 356.01; FT IR (v cm-1) 3146, 3040, 2939, 2842,
1609, 1537, 1482, 1252, 1025. 1H NMR (CDCl3, 400 MHz)
d 3.84 (s, 3H, –OCH3), 4.96 (s, 2H, –CH2–), 6.96 (d, J =
8 Hz, 2H), 7.27 (d, J = 8 Hz, 2H), 7.36 (d, J = 8 Hz, 2H),
7.73 (d, J = 8 Hz, 2H), 7.88 (s, 1H, im).
2-Benzyl-6-(4-methoxyphenyl)imidazo
[2,1-b][1,3,4]thiadiazole (4Ac)
2-(4-Chlorobenzyl)-6-(4-nitrophenyl)imidazo
[2,1-b][1,3,4]thiadiazole (4Bd)
MS m/z 322.10; FT IR (v cm-1) 3133, 3062, 2960, 2910,
1611, 1522, 1488, 1430, 1244. 1H NMR (CDCl3,
400 MHz) d 3.84 (s, 3H, –OCH3), 4.33 (s, 2H, –CH2–),
6.97 (d, J = 8 Hz, 2H), 7.31–7.41 (m, 5H), 7.74 (d, J =
8 Hz, 2H), 7.88 (s, 1H, im).
MS m/z 369.00; FT IR (v cm-1) 3130, 2925, 2832, 1597,
1504, 1414, 1338, 1266, 1098. 1H NMR (CDCl3, 400 MHz)
d 4.47 (s, 2H, –CH2–), 7.44 (m, 4H), 8.09 (d, J = 8 Hz, 2H),
8.26 (d, J = 8 Hz, 2H), 8.91 (s, 1H, im).
2-(4-Chlorobenzyl)-6-(4-bromophenyl)imidazo
[2,1-b][1,3,4]thiadiazole (4Be)
2-Benzyl-6-(4-nitrophenyl)imidazo
[2,1-b][1,3,4]thiadiazole (4Ad)
MS m/z 405.90; FT IR (v cm-1) 3149, 3055, 2927, 2865,
1590, 1528, 1476, 1401, 1082. 1H NMR (CDCl3, 400 MHz)
d 4.27 (s, 2H, –CH2–), 7.27 (d, J = 8 Hz, 2H), 7.37 (d, J =
8 Hz, 2H), 7.53 (d, J = 8 Hz, 2H), 7.68 (d, J = 8 Hz, 2H),
7.96 (s, 1H, im).
MS m/z 337.00; FT IR (v cm-1) 3132, 3074, 2931, 2830,
1600, 1504, 1469, 1339, 1029. 1H NMR (CDCl3, 400 MHz)
d 4.46 (s, 2H, –CH2–), 7.29–7.42 (m, 5H), 8.10 (d, J =
8 Hz, 2H), 8.27 (d, J = 8 Hz, 2H), 8.92 (s, 1H, im).
2-(4-Nitrobenzyl)-6-(4-chlorophenyl)imidazo
[2,1-b][1,3,4]thiadiazole (4Ca)
2-Benzyl-6-(4-bromophenyl)imidazo
[2,1-b][1,3,4]thiadiazole (4Ae)
MS m/z 371.01; FT IR (v cm-1) 3077, 3038, 2939, 2846,
1601, 1598, 1518, 1341, 1093. 1H NMR (CDCl3, 400 MHz)
d 4.65 (s, 2H, –CH2–), 7.47 (d, J = 8 Hz, 2H), 7.72 (d, J =
8 Hz, 2H), 7.87 (d, J = 8 Hz, 2H), 8.26 (d, J = 8 Hz, 2H),
8.71 (s, 1H, im).
MS m/z 372.00; FT IR (v cm-1) 3148, 3060, 3026, 2964,
1
2826, 1517, 1480, 1397, 1256, 1004. H NMR (CDCl3,
400 MHz) d 4.30 (s, 2H, –CH2–), 7.31–7.41 (m, 5H), 7.52
(d, J = 8 Hz, 2H), 7.68 (d, J = 8 Hz, 2H), 7.96 (s, 1H, im).
2-(4-Chlorobenzyl)-6-(4-chlorophenyl)imidazo
[2,1-b][1,3,4]thiadiazole (4Ba)
2-(4-Nitrobenzyl)-6-(4-methylphenyl)imidazo
[2,1-b][1,3,4]thiadiazole (4Cb)
MS m/z 360.00; FT IR (v cm-1) 3147, 3057, 2927, 2861,
1528, 1476, 1403, 1092. 1H NMR (CDCl3, 400 MHz) d 4.27
(s, 2H, –CH2–), 7.27 (d, J = 8 Hz, 2H), 7.35–7.38 (dd,
J = 8, 8 Hz, 4H), 7.72 (d, J = 8 Hz, 2H), 7.94 (s, 1H, im).
MS m/z 350.01; FT IR (v cm-1) 3140, 3073, 2962, 2861,
1
1522, 1460, 1347, 1178. H NMR (CDCl3, 400 MHz) d
2.31 (s, 3H, –CH3), 4.64 (s, 2H, –CH2–), 7.22 (d, J =
8 Hz, 2H), 7.71 (d, J = 8 Hz, 2H), 7.74 (d, J = 8 Hz, 2H),
8.26 (d, J = 8 Hz, 2H), 8.59 (s, 1H, im).
2-(4-Chlorobenzyl)-6-(4-methylphenyl)imidazo
[2,1-b][1,3,4]thiadiazole (4Bb)
2-(4-Nitrobenzyl)-6-(4-nitrophenyl)imidazo
[2,1-b][1,3,4]thiadiazole (4Cd)
MS m/z 340.00; FT IR (v cm-1) 3143, 3055, 3021, 2961,
2924, 2865, 1596, 1535, 1461, 1290, 1935. 1H NMR (CDCl3,
MS m/z 382.00; FT IR (v cm-1) 3126, 3087, 2938, 2845,
1601, 1517, 1341, 1101, 1009. 1H NMR (CDCl3,
400 MHz)
d 2.37 (s, 3H, –CH3), 4.26 (s, 2H,
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Med Chem Res (2012) 21:1550–1556
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400 MHz) d 4.67 (s, 2H, –CH2–), 7.72 (d, J = 8 Hz, 2H),
8.11 (d, J = 8 Hz, 2H), 8.25 (d, J = 8 Hz, 2H), 8.28 (d, J =
8 Hz, 2H), 8.94 (s, 1H, im).
Results and discussion
Chemistry
2-(4-Nitrobenzyl)-6-(4-bromophenyl)imidazo
[2,1-b][1,3,4]thiadiazole (4Ce)
2-Amino-5-substituted-1,3,4-thiadiazoles 3 were prepared
from aryl acetic acid 1 and thiosemicarbazide 2 in H2SO4
heating at 70°C for 7 h (Table 1). The various a-bromo
ketones were prepared by bromination of the corresponding
ketones using the Friedel–Crafts reaction (Blatt 1943). The
2-(4-substituted phenyl)-6-(4-substituted aryl)-imidazo[2,1-b]
[1,3,4]thiadiazole derivatives 4 have been reported in
Scheme 1 and Tables 2 3, and 4 were prepared by conden-
sation of 3 with the appropriate a-bromo ketone, under reflux
(8–10 h) and neutralization with cold aqueous sodium car-
bonate to get the free base in 40–60% yield. Using MW
technique in DMF, and remaining contents are other wise
same, desired products are obtained in good yield in less time
(4–7 min). It is well estimated that these reactions proceed
via the intermediate iminothiadiazole (Gadad et al., 2000)
which further undergoes dehydrocyclization to form the
MS m/z 414.90; FT IR (v cm-1) 3073, 2936, 1598, 1342,
1
1177. H NMR (CDCl3, 400 MHz) d 4.65 (s, 2H, –CH2–),
7.60 (d, J = 8 Hz, 2H), 7.72 (d, J = 8 Hz, 2H), 7.81 (d, J =
8 Hz, 2H), 8.26 (d, J = 8 Hz, 2H), 8.72 (s, 1H, im).
2-(4-Nitrobenzyl)-6-(4-fluorophenyl)imidazo
[2,1-b][1,3,4]thiadiazole (4Cf)
MS m/z 355.03; FT IR (v cm-1) 3122, 3077, 2914, 2855,
1601, 1522, 1348, 1227, 1099. 1H NMR (CDCl3,
400 MHz) d 4.63 (s, 2H, –CH2–), 7.19–7.25 (m, ar, 2H),
7.71 (d, J = 8 Hz, 2H), 7.84–7.89 (m, 2H), 8.25 (d, J =
8 Hz, 2H), 8.63 (s, 1H, im).
Table 1 Physicochemical data for the derivatives (3A–3C)
R
N
N
H2N
S
Code no
R
Yield (%)
MP (oC)
Molecular formula
Rf
Molecular weight
3A
3B
3C
H
55–60
55–60
50–55
201–203
180–182
181–183
C9H9N3S
0.71
0.69
0.60
192.15
225.70
237.14
Cl
C9H8N3SCl
C9H8O2N4S
NO2
Scheme 1 R = benzyl (A),
4-chloro benzyl (B), 4-nitro
benzyl (C). R0 = Cl (a), CH3
(b), OCH3 (c), NO2 (d),
Br (e), F (f)
N
N
H2N
NH
O
H2SO4
+
R
70-80 0C
NH2
NH2
S
R
OH
S
3
2
1
10-12 Hrs
MW
EtOH
4-7 min
i) R'-C6H4-COCH2Br
ii) Na2CO3
N
N
R
R'
S
N
4
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Med Chem Res (2012) 21:1550–1556
Table 2 Physicochemical parameters of synthesized derivatives
Table 4 Antibacterial and antifungal activities of the compounds
(4Ba–4Be and 4Ca–4Ce)
Code no
R
R0
Molecular
formula
Rf
Molecular
weight
Comp. code
S. aureus
Klebsiella
C. albicans
4Aa
4Ab
4Ac
4Ad
4Ae
4Ba
4Bb
4Bc
4Bd
4Be
4Ca
4Cb
4Cd
4Ce
4Cf
H
Cl
C17H12N3SCl
C18H15N3S
0.78
0.76
0.69
0.63
0.86
0.74
0.35
0.78
0.67
0.53
0.72
0.30
0.65
0.64
0.48
325.82
305.40
321.40
336.37
370.27
360.27
339.85
355.85
370.82
404.72
370.82
350.40
381.37
415.27
354.36
4Ba
–
50(12)
–
50(12)
H
CH3
OCH3
NO2
Br
4Bb
–
–
H
C18H15ON3S
C17H12N4SO2
4Bc
75(15)
–
75(12)
H
4Bd
75(12)
50(14)
50(12)
50(12)
50(12)
50(16)
5(14)
–
–
H
C
C
17H12N3SBr
17H11N3SCl2
4Be
–
50(14)
Cl
Cl
4Ca
–
–
Cl
CH3
OCH3
NO2
Br
C18H14N3SCl
4Cb
–
–
Cl
C18H14ON3SCl
C17H11O2N4SCl
4Cd
–
–
Cl
4Ce
–
–
Cl
C
17H11N3SClBr
4Cf
–
50(22)
–
NO2
NO2
NO2
NO2
NO2
Cl
C17H11O2N4SCl
C18H14O2N4S
C17H11O4N5S
C17H11O2N4SBr
C17H11FN4O2S
Ciprofloxacin
Fluconazole
Control
10(28)
–
10(28)
–
CH3
NO2
Br
30(22)
DMSO
DMSO
DMSO
Zone of inhibition in millimeters and MIC values (mean of triplicates)
MIC values are given in brackets
F
– not active
Table 3 Comparative reaction time and melting points of the syn-
thesized compounds
spectra displayed a D2O exchangeable peak due to NH2 at
d 7.08–7.12 ppm. Structures of imidazothiadiazole deriv-
atives were established by the absence of vN–H band in the
IR spectra and appearance of imidazole proton (C5-H)
around d 7.94–8.94 ppm in the 1H NMR spectra. The mass
spectra of these compounds further confirmed the assigned
structures.
Code no MW (min) Conv (h) Yields (%) MP (°C)
MW Conv MW
Conv
4Aa
4Ab
4Ac
4Ad
4Ae
4Ba
4Bb
4Bc
4Bd
4Be
4Ca
4Cb
4Cd
4Ce
4Cf
4
5
7
5
5
4
6
4
5
5
4
5
5
4
4
85
75
84
83
80
84
80
75
83
78
75
75
82
80
82
45
48
51
55
48
52
50
60
55
57
60
55
52
60
55
159–162 165–168
140–142 142–144
158–161 160–163
233–235 231–233
162–163 160–162
174–176 178–179
180–183 178–181
171–173 174–176
192–194 195–198
160–162 164–165
178–180 178–181
175–177 173–175
216–218 215–218
180–181 186–188
181–184 179–182
Antimicrobial activity
The newly synthesized compounds were screened for their
antibacterial and antifungal activity using cup plate method
(Revol-Junelles et al., 1996). The antibacterial activity of
test compounds was evaluated against Staphylococcus
aureus and Klebsiella, and ciprofloxacin was used as
standard drug. Antifungal activity was screened against
Candida albicans using fluconazole as standard drug, and
dimethyl formamide was used as solvent control.
8–10
The bacterial cultures were inoculated on Mueller–
Hinton Agar (Merck), fungal culture was inoculated on
Potato Dextrose Agar, and Media (20 ml) were poured into
each sterilized Petri dish (99 mm). Media plates were
inoculated with liquid cultures homogenously by spread
plate method.
MW microwave method; Conv conventional method
MP melting point; min minutes; h hours
desired fused heterocyclic (Scheme 1) derivative (4Aa–
4Cf). The IR and 1H NMR spectra of the synthesized com-
pounds are in agreement with the assigned structures.
The formation of 2-amino thiadiazole 3 by the reaction
was confirmed by its IR spectrum, which showed the
presence of vN–H band and the absence of the carbonyl
stretching band of carboxylic acid. Further, 1H NMR
All compounds were dissolved in DMSO to get a desired
concentration. Each sample was loaded into the wells of
agar plates directly. Plates inoculated with bacteria were
incubated at 37°C for 24 h, and fungal culture was incubated
at 25°C for 72 h. All determinations were done in tripli-
cates. The standard antibiotic ciprofloxacin (10 lg/ml) for
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1555
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The investigation of antibacterial screening revealed
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S. aureus by 15 and 12 mm at 75 lg/ml, respectively, on
comparing to standard ciprofloxacin 28 mm at 10 lg/ml.
Where as 4Ce showed antibacterial activity against Kleb-
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4Cd, and 4Ce were showed mild to moderate activity
against Klebsiella microorganism at C50 lg/ml.
Antifungal result indicated that compound 4Ba, 4Be,
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Conclusion
We have synthesized 15 derivatives of 2,6-disubstituted
imidazo[2,1-b][1,3,4]thiadiazoles by conventional and
MW technique. MW technique demonstrated the benefits
like convenient operation, short reaction time, and good
yields. 4Cf was the lonely compound which showed good
antifungal activity comparable to that of standard fluco-
nazole at 50 lg/ml. The results of antibacterial screening
reveal that among all the compounds screened 4Ba, 4Be,
4Ca, 4Cd, and 4Cb showed mild activity at 50 lg/ml
against S. aureus microorganism. Only 4Ce had showed
mild antibacterial activity at low micromolar concentration
(5 lg/ml) against S. aureus. Most of these compounds were
sensitive towards Klebsiella microorganism.
Acknowledgment Authors are thankful to Dr. B. G. Desai, Prin-
cipal, KLE University’s College of Pharmacy, Bangalore for pro-
viding necessary facilities. We gratefully acknowledge the support for
this research effort from All India Council for Technical Education
(AICTE), New Delhi (Ref. No. 8023/BOR/RID/RPS-169/2008-09).
The authors are also grateful to NMR research centre, Indian Institute
of Science, Bangalore, India for recording NMR spectra for our
compounds.
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