Synthesis and characterization of thiazole and 2-thioxoimidazolidinone derivative; Their antibacterial and anticancer properties

Article abstract of DOI:10.1007/s11164-012-0911-4

5-Aryl-2-[(5-substituted-3-methoxy-2-hydroxybenzylidene)-hydrazine] -thiazoles (3a,b) and 3-[(5-substituted-3-methoxy-2-hydroxybenzylidene)amino]-4- oxo-imidazolidin-2-thiones (4a,b) were prepared via cyclization of 5-substituted-3-methoxy-2-hydroxy-benza

Full text of DOI:10.1007/s11164-012-0911-4

Res Chem Intermed
DOI 10.1007/s11164-012-0911-4
Synthesis and characterization of thiazole
and 2-thioxoimidazolidinone derivative;
their antibacterial and anticancer properties
•
Mohamed H. Sherif Ibrahim M. Eldeen
Eman O. Helal
•
Received: 10 October 2012 / Accepted: 4 November 2012
Ó Springer Science+Business Media Dordrecht 2012
Abstract 5-Aryl-2-[(5-substituted-3-methoxy-2-hydroxybenzylidene)-hydrazine]-
thiazoles (3a,b) and 3-[(5-substituted-3-methoxy-2-hydroxybenzylidene)amino]-4-
oxo-imidazolidin-2-thiones (4a,b) were prepared via cyclization of 5-substituted-3-
9
methoxy-2-hydroxy-benzaldehyde thiosemicarbazones (2a,b) with x-bromomethyl
aryl ketones and ethyl chloroacetate in fused sodium acetate. Acetylation of thia-
zoles and imidazolidinone derivatives with acetic anhydride yielded the diacetyl
derivatives (5a,b and 6a,b). Acetylation of 4 with acetic anhydride in fused sodium
acetate gave the corresponding triacetyl derivatives (7a,b). Synthesized compounds
were characterized by EI-MS and NMR spectroscopy. The biological activity
studies of thiazoles and imidazolidinone were carried out against antimicrobial and
anticancer activities.
Keywords Imidazolidine ꢀ Thiosemicarbazide ꢀ
Antimicrobial and anticancer activities
Introduction
Sulpha drugs are well recognized for various physiological activities [1, 2], and
antibacterial, fungicidal, and pesticidal properties [3], while imidazolidines and
thiazoles have been associated with various biological activities [4–8]. In a previous
work, El-Deen and coworkers [9–11] reported the synthesis of thiazoles and
9
imidazolidinone with x-bromomethyl aryl ketones and ethyl chloroacetate. This
M. H. Sherif (&) ꢀ E. O. Helal
Department of Chemistry, Faculty of Science, Zagazig University, Zagazig, Egypt
e-mail: meahsherif@hotmail.com
I. M. Eldeen
Department of Chemistry, Faculty of Science, Port Said University, Port Said, Egypt
123

M. H. Sherif et al.
paper describes the synthesis of thiazoles (3) and imidazolidinone (4) from
condensation of 5-substituted-3-methoxy-2-hydroxybenzaldehydes (1a,b) with thio-
semicarbazide which gave 5-substituted-3-methoxy-2-hydroxybenzaldehyde thio-
9
semicarbazones (2a,b), followed by cyclization of 2 with with x-bromomethyl aryl
ketones and ethyl chloroacetate in fused sodium acetate. The EIMS fragmentation
pattern and NMR data of the synthesized compounds is also discussed.
Chemistry
Synthesis
The synthetic pathways leading to the new thiazole and imidazolidinone derivatives
are illustrated in Scheme 1. Condensation of 5-substituted-3-methoxy-2-hydro-
xybenzaldehydes (1a,b) with thiosemicarbazide and gave 5-substituted-3-methoxy-
2-hydroxybenzaldehyde thiosemicarbazones (2a,b). Treatment of compound 2 with
9
x-bromomethyl aryl ketones, such as (4-methylphenacyl bromide and 4-methoxy
phenacyl bromide) and ethyl chloroacetate in sodium acetate in methanol under
reflux, yielded the corresponding 5-aryl-2-[(5-substituted-3-methoxy-2-hydroxy-
benzylidene)-hydrazineo]-thiazoles (3a,b) and 3-[(5-substituted-3-methoxy-2-
hydroxybenzylidene) amino]-4-oxo-imidazolidin-2-thiones (4a,b).
Acetylation of compounds 3 and 4 with acetic anhydride under reflux led to the
formation 5-aryl-2-[(5-substituted-3-methoxy-2-acetoxybenzylidene)-acetyl-hydra-
zino]-thiazoles (5a,b) and 1-acetyl-3-[(5-substituted-3-methoxy-2-acetoxy-benzyli-
dene) amino]-4-oxo-imidazolidin-2-thione (6a,b). 1,5-Diacetyl-3-[(5-substituted-3-
methoxy-2-acetoxy-benzylidene) amino]-4-oxo-imidazolidin-2-thiones (7a,b) were
prepared via acetylation [12] of compound 4 with acetic anhydride in the presence
of fused sodium acetate under reflux.
Mass spectrometry
After studying the MS fragmentation pattern, different fragmentation pathways
were suggested which are discussed in the following paragraphs [13, 14].
Compounds 3 and 5
The mass spectra of synthesized compounds 3(a,b) (Fig. 1), 5a (Fig. 3) and 5b
showed intense molecular ion peaks at m/z 339, 433/435, 423, and 517/519
consistent with the molecular formulae C18H17N3O2S, C18H16N3BrO3S,
C22H21O4S, and C22H20N3BrO5S, respectively. The molecular ion of compounds
3(a,b) fragmented to produce stable ions at m/z 322 and m/z 416 after losing the
hydroxyl group (OH). The fragment ions at m/z 322 and m/z 416 fragmented via the
suggested pathways A to a fragment of ions at m/z 190 and m/z 206, corresponding
to the molecular ion of 5-(4-alkylphenyl)-2-aminothiazole. It underwent further loss
of NH2CN, S, and acetylene C2H2 and gave peaks at m/z 148, 164, m/z 116, 132, and
123

Synthesis and characterization of thiazole
X
CHO
OH
OCH3
1
a,X=H ; b,X=Br
NH2NHCSNH2
MeOH
X
N-NHCSNH2
OH
OCH3
2
ClCH2COOEt
Ar-COCH2Br
MeOH \ ACONa
MeOH \ ACONa
S
S
X
X
Ar
N-NH
N
O
N
NH
N
OH
OH
OCH3
OCH3
4a,b
3a,b
AC2O
AC2O
AC2O /
ACONa
S
X
N
N
N-COCH3
X
COCH3
S
OCOCH3
O
Ar
NH-N
OCOCH3
OCH3
N
6
OCH3
5
S
X
N
N
O
a,X=H, Ar= C6H4CH3- P
b,X=Br, Ar= C6H4OCH3- P
N-COCH3
COCH3
OCOCH3
OCH3
7
a,X =H
b,X =Br
Scheme 1 Heterocyclization of arylsemicarbazone
123

M. H. Sherif et al.
m/z 91, 107, respectively. The fragment ions at m/z 322 and 416 were also found to
undergo fragmentation via pathway B to produce the ions of m/z 132 and 210, which
further fragmented and gave a fragment of ions at m/z 106 and m/z 184 by losing the
cyano group (CN). The ions of m/z 106 and m/z 184 were broken and gave the ions
of m/z 76 and 154 by losing the formaldehyde molecule. The diacetyl derivatives
5(a,b) were broken and gave fragment ions at m/z 381 and 475 by losing the ketene
molecule (CH2CO). The loss of the ketene molecule from the fragment ions at m/
z 381 and 475 gave a fragment of ions at m/z 339 and m/z 433, corresponding to the
molecular ion of compounds 3(a,b), respectively. The fragment ions at m/z 339 and
m/z 433 broke further via a pathway similar to compounds 3(a,b) (Scheme 2).
Compounds 4, 6 and 7
The mass spectra of compounds 4(a,b) were fully consistent with the assigned
structures. In most cases, intense molecular ion peaks were observed. Thus,
compounds 4(a,b) showed intense molecular ion peaks at m/z 265 and m/z 343/345,
corresponding to the molecular formulae C11H11N3O3S and C11H10N3BrO3S,
respectively. The molecular ion of m/z 265 and 343 fragmented via the pathway
A and gave the stable ion of m/z 248 and ion of m/z 326 by losing the hydroxyl
group (OH). The fragment ions of m/z 248 and m/z 326 were broken to give
fragment ions of m/z 219 and m/z 297 which lost the formyl group (CHO). The
fragmentation led to ions of m/z 177, 255; m/z 162, 240; m/z 117, 195, and m/z 89,
167, respectively. Accordingly, the same molecular ion of m/z 265 and 343
fragmented via the pathway B to give a fragmentation of m/z 150 and m/z 228, and it
underwent further loss of NH and the two-formyl group (CHO) and gave peaks at
m/z 135, 213; m/z 106, 184, and m/z 77, 155, respectively. Also, the same molecular
ion of m/z 265 and m/z 343 fragmented with rearrangement via pathway C and gave
the ion of m/z 116, corresponding to 2-thioxo-imidazolidin-2-thione. The molecular
ion peaks of compounds 6(a, b) were observed at m/z 349 and 427/429,
corresponding to molecular formulae C15H15N3O5N and C15H14N3BrO5S, respec-
tively. The loss of the ketene molecule (CH2CO) from the molecular ion peaks at
m/z 349 and m/z 427 gave peaks at m/z 307 and m/z 385. The fragment ions of m/
z 307 and 385 fragmented to give a peak at m/z 265, 343, corresponding to the
molecular ion of compounds 4(a,b) by losing the ketene molecule. The molecular
ion triacetyl derivatives 7(a,b) were observed at m/z 391 and 469/471, correspond-
ing to the molecular formulae C17H17N3O6N and C17H16N3BrO6S, respectively
(Schemes 3 and 4).
The loss of the ketene molecule from the molecular ion peaks at m/z 391 and 469
gave peaks at m/z 349 and 427, corresponding to molecular ion peaks of compound
6(a,b), respectively. The EIMS of compounds 4a, 6a showed a base peak of
m/z 279. The mass spectra of compounds 4b, 6b and 7b showed a base peak at
m/z 76, 325 and m/z 63 (Figs. 1, 2, 3, 4, 5).
123

Synthesis and characterization of thiazole
Scheme 2 Fragmentation
pattern of thiazole 3 and 5
COCH3
X'
S
NH-N
OCOCH3
X
N
OCH3
a,X=CH3
; X'=H ;m/z 423 (8.9 %)
b,X=OCH3; X'=Br ; m/z 517(89.30%)
5
-
CH2CO
H
S
N
X'
NH-N
X
OCOCH3
OCH3
a,X=CH3
; X'=H ;m/z 381 (30.40 %)
b,X=OCH3; X'=Br ; m/z 475(81.14%)
-
CH2CO
H
S
N
X'
NH-N
X
OH
OCH3
a,X=CH3
; X'=H ;m/z 339 (20.30%)
b,X=OCH3; X'=Br ; m/z 433(55.50%)
3
-
OH
H
S
X'
NH-N
X
N
OCH3
a,X=CH3
; X'=H ;m/z 322 (100%)
b,X=OCH3; X'=Br ; m/z 416(92.31%)
Pathway
Pathway
A
B
S
X'
H2
N
X
N
N
OCH3
a,X=CH3 ;m/z 190(89.90%)
b,X=OCH3; m/z 206(100%)
a,X'=H ;m/z 132(15.20%)
b,X'=Br; m/z 210(16.80%)
123

M. H. Sherif et al.
Scheme 2 continued
-
NH2-CN
-CN
S
X'
X
OCH3
a,X=CH3 ;m/z 148 (64.60%)
b,X=OCH3; m/z 164(39.79%)
a,X'=H ;m/z 106(11.40%)
b,X'=Br; m/z 184(11.27%)
-
S
-CH2O
X'
HC
C
X
a,X=CH3 ;m/z 116 (22.80%)
b,X=OCH3; m/z 132(5.95%)
a,X'=H ;m/z 76(27.80%)
b,X'=Br; m/z 154(13.20%)
-C2H
x
a,X=CH3 ;m/z 91 (34.20%)
b,X=OCH3; m/z 107 (5.93%)
Biological assay
Antimicrobial activity
All the compounds 3–6 were in vitro screened for their antibacterial activity against
Gram-positive [Bacillus subtilis (RCMBOOO107), Streptococcus pneumonia
(RCMBOOO105), Staphylococcus aureus (RCMBOOO106)] and Gram-negative
[Escherichia coli (RCMBOOO103) and Pseudomonas sp. ATCC 9027] bacteria by
the drug diffusion method [15]. The zone of inhibition was measured in mm and
was compared with standard drugs. DMSO was used as a blank and streptomycin
was used as antibacterial standard. All the compounds were tested at 50, 100, and
150 mg concentrations. The data are summarized in Table 1, and show that all
compounds display certain antibacterial activity.
Anticancer activity
The cytotoxic and antitumor activities of prepared compounds 3–7 were tested against
the MCF-7 and HePG2 cell lines according to the method of Masmann [16] and
123

Synthesis and characterization of thiazole
S
X
-
OH
N
O
N
NH
OH
OCH3
C
A
a, X= H; m/z 265( 76.20 %)
b, X =Br; m/z 343 (60.00 %)
S
S
-
C3H3N2OS
B
X
N
O
N
NH
HN
NH
O
OCH3
X
NH2
m/z 116(50.00%)
O
a, X= H; m/z 248( 100 %)
b, X =Br; m/z 326 (76.60%)
-CH2CO
OCH3
-CHO
a, X= H; m/z 150
b, X =Br; m/z 228(22.00)
S
S
-NH
HN
NH
X
N
N
NH
O
m/z 79(31.30%)
X
O
a, X= H; m/z 219( 16.20%)
b, X =Br; m/z 297
OCH3
-
CH2CO
a, X= H; m/z 135 (36.80%)
b, X =Br; m/z 213(18.20 %)
-CHO
N
N
X
X
HN
S
OCH3
a, X= H; m/z 177( 21.30%)
b, X =Br; m/z 255
a, X= H; m/z 106(41.90%)
b, X =Br; m/z 184(17.20 %)
-NH
-CHO
X
N
N
X
S
a, X= H; m/z 162( 23.50%)
b, X =Br; m/z 240
a, X= H; m/z 77(37.50%)
b, X =Br; m/z 155(10.10%)
-
CHS
X
N
X
N
-N2
a, X= H; m/z 117( 25.50%)
b, X =Br; m/z 195
a, X= H; m/z 84( 33.40%)
Scheme 3 Fragmentation pattern of compound 4
123

M. H. Sherif et al.
S
Scheme 4 Fragmentation
pattern of compounds 6 and 7
X
N
N
N-COCH3
OCOCH
3 O
COCH3
OCH3
7
a,X =H, m/z 391(21.30%)
b,X =Br, m/z 469
-CH2CO
S
X
N
N
N-COCH3
OCOCH
3 O
OCH3
a,X =H, m/z 349 (7.90%)
b,X =Br, m/z 427(12.10%)
-CH2CO
S
X
N
N
N-COCH3
OH
OCH3
O
a,X =H, m/z 307 (22.71%)
b,X =Br, m/z 385(56.10%)
-
CH2CO
S
X
N
N
O
N-H
OH
OCH3
a,X =H, m/z 265 (76.20%)
b,X =Br, m/z 343(60.00%)
123

Synthesis and characterization of thiazole
Fig. 1 EIMS spectrum of compound 3b
Fig. 2 EIMS spectrum of compound 4a
Fig. 3 EIMS spectrum of compound 5a
Fig. 4 EIMS spectrum of compound 6a
123

M. H. Sherif et al.
Fig. 5 EIMS spectrum of compound 7a
MCF-7
120
100
80
60
40
20
0
3a
3b
4a
4b
5a
concentration (mg)
Fig. 6 The inhibitory activities against breast carcinoma cells
Vijayan et al. [17]. The inhibitory activities against breast carcinoma cells (MCF-7 cell
line) and hepatocellular carcinoma cells (HePG2 cell line) were detected by using
different concentrations of the tested compounds (50, 25, 12.5, 6.25, 3.125, and
1.56 mg), and the viability cells (%) were determined by the colorimetric method.
Also, the (IC50) was calculated from Tables 2, 3 and Figs. 6, 7, 8, and 9.
Table 4 summarizes the results of cytotoxicity testing against human breast
carcinoma cells lines and heptocellular carcinoma cells lines (IC50).
The results revealed that all tested compounds have cytotoxic and antitumor
activity against the breast carcinoma cell line and the hepatocellular carcinoma cell
line except compounds 3b, 5b and 7a. Compound 4a (IC50 14.50 mg, IC50 6.90 mg)
and compound 5a (IC50 12.00 mg, IC50 9.90 mg) are the best.
Conclusion
In this work, the synthesis and antimicrobial and the anticancer activities of new
thiazole and 2-thioxoimidazolidine derivatives 3–7 are described. The compounds
showed in vitro growth inhibitory activities against the tested organisms including
higher than streptomycin. Compounds 4a and 5a are more potent than the other
123

Synthesis and characterization of thiazole
123

M. H. Sherif et al.
MCF-7
120
100
80
60
40
20
0
5b
6a
6b
7
concentration (mg)
Fig. 7 The inhibitory activities against breast carcinoma cells
Table 2 Evaluation of cytotoxicity against MCF-7 cell line
Sample conc. (mg) Viability (%)
3a
3b
4a
4b
5a
5b
5a
6b
7
50
27.56 79.62
39.98 90.44
54.32 97.76
25.62
37.36
52.48
42.70 16.28 71.24 40.82 18.76 58.94
59.86 29.46 86.48 61.44 34.28 71.28
71.52 43.32 95.86 74.56 62.53 87.36
25
12.5
6.25
3.125
1.56
0
69.47 100.00 61.73
80.26 100.00 73.44
91.84 100.00 86.62
83.38 59.60 100
90.84 72.43 100
96.35 88.12 100
86.93 80.42 96.12
96.75 91.55 100
100
100
98.14 100
100
100.00 100.00 100
100
100
100
100
Table 3 Evaluation of cytotoxicity against HePG2 cell line
Sample conc. (mg)
Viability (%)
3a
3b
4a
4b
5a
5b
6a
6b
7
50
33.82
45.70
62.38
79.45
90.10
98.32
100
68.74
80.18
91.50
98.63
100
13.98
22.86
38.12
51.38
67.29
81.56
100
39.44
58.68
69.40
78.42
89.23
96.14
100
21.18
32.92
48.64
63.58
79.14
92.53
100
62.48
80.52
89.36
98.92
100
30.58
48.72
63.40
76.94
85.58
93.79
100
31.94
41.53
70.48
82.13
91.86
97.98
100
59.13
68.74
80.36
89.97
96.59
100
25
12.5
6.25
3.125
1.56
0
100
100
100
100
100
compounds against human breast carcinoma cell line and hepatocellular carcinoma
cell line. The biological data revealed that, with slight modifications in the structure,
one can plan for the drug design.
123

Synthesis and characterization of thiazole
HepG2
120
100
80
60
40
20
0
3a
3b
4a
4b
5a
concentration (mg)
Fig. 8 The inhibitory activities against hepatocellular carcinoma cells
HepG2
120
100
80
60
40
20
0
5b
6a
6b
7
concentration (mg)
Fig. 9 The inhibitory activities against hepatocellular carcinoma cells
Experimental
NMR spectra were recorded on a General Electric QE 300 instrument and chemical
shifts are given in d (ppm) with TMS as internal references. IR spectra were recorded
on Perkin-Elmer 1420 and Biorad FTS 7 spectrometers in KBr pellets. Mass spectra
were obtained on a Jeol JMS D-300 spectrometer operating at 70 eV. Microanalyses
were conducted using a 1106 elemental analyzer. Melting points were uncorrected and
were determined on Gallenkamp electric melting point apparatus.
5-Substituted-3-methoxy-2-hydroxy-benzaldehyde thiosemicarbazones (2a,b)
A mixture of 1 (0.01 mol) and thiosemicarbazide (0.01 mol) in methanol (30 ml)
was heated under reflux for 4 h, then cooled. The solid formed was filtered off, dried
and purified by recrystallization from ethanol to give 2.3-methoxy-2-hydroxyben-
zaldehyde thiosemi-carbazone 2a as pale yellow crystals, yield 78 %, m.p. 250 °C.
123

M. H. Sherif et al.
IR (KBr): 3,500–2,842 (br-OH), 3,456, 3,163 (NH2), 3,344 (NH), 1,615 (C=N),
1
1,326 (C=S), 1,211, 1,056 (C–O)cm-1. H-NMR (CDCL3): d 3.94 (s,3H,OCH3),
6.89 (s,2H,NH2), 7.12–7.51 (m,3H,Ar–H), 7.81 (s,1H,CH=N), 9.92 (s,1H,NH),
11.14 (s,1H,OH) ppm. MS: (m/z, %): 226 (M??1, 12.5), 255 (M?, 100), 223 (7.60),
209 (2.70), 208 (7.6), 194 (3.90), 193 (2.50), 180 (2.40), 179 (1.50), 166 (2.00),165
(5.50), 164 (4.70),152 (6.90),151 (5.90), 150 (33.90), 149 (25.30), 148 (18.80), 137
(9.90), 135 (22.20), 134 (9.90), 133 (8.50), 132 (6.80), 131 (9.70), 130 (5.90), 121
(9.90), 120 (8.60),119 (8.60), 109 (5.40), 108 (12.90), 107 (12.20), 106 (20.00), 105
(16.60), 102 (11.80), 94 (6.80), 93 (12.80), 92 (8.80), 91 (7.30), 79 (16.20), 78
(18.00), 77 (61.70), 76 (33.50), 75 (24.00), 66 (10.80), 65 (28.00), 64 (12.30), 63
(16.20), 60 (49.50), 59 (14.80), 53 (22.20), 52 (29.90), 51 (35.20), 50 (19.50). Anal.
Found: C, 47.89; H, 4.68; N, 18.52; S, 14.02. C9H11N3O2S requires: C, 48.00; H,
4.89; N, 18.67; S, 14.22.
5-Bromo-3-methoxy-2-hydroxybenzaldehyde thiosemicarbazone 2b as pale
yellow crystals, yield 73 %, m.p. 220 °C. IR (KBr): 3,550–2,980 (br.OH), 3,452,
3,106 (NH2), 3,325 (NH), 1,616 (C=N), 1,535 (C=C), 1,365 (C=S), 1,249, 1,064 (C–
1
O)cm-1. H-NMR (CDCl3): d 3.97 (s,3H,OCH3), 6.74 (s,2H,NH2),7.26 (s,1H,Ar–
H),7.73 (s,1H,Ar–H), 8.37 (s,1H,CH=N), 9.83 (s,1H,NH), 11.01 (s,1H,OH) ppm.
MS: (m/z, %): 305 (M??2,21.90), 304 (M??1,10.40), 303 (M?,10.40), 296 (6.30),
295 (8.30), 293 (11.50), 292 (10.40), 291 (8.30), 290 (12.50), 289 (11.50), 288
(11.50), 266 (19.80), 264 (15.60), 263 (13.50), 261 (10.40), 245 (6.30), 244 (17.70),
243 (11.50), 230 (18.70), 229 (29.20), 228 (28.10), 227 (31.30), 217 (14.60), 215
(18.80), 214 (14.60), 213 (10.40), 211 (11.50), 200 (11.50), 199 (13.50), 197 (7.30),
186 (28.10), 185 (18.80), 184 (14.60), 183 (12.50), 181 (13.50), 171 (11.50), 164
(12.10), 158 (14.60), 157 (16.70), 156 (11.50), 145 (10.40), 144 (12.50), 143
(10.40), 141 (16.70), 134 (11.50), 133 (16.70), 131 (10.40), 130 (10.40), 122
(19.80), 121 (11.50), 120 (13.50), 119 (18.80), 118 (15.60), 117 (12.10), 107
(16.70), 106 (12.50), 105 (25.00), 104 (26.00), 103 (14.60), 102 (28.10), 94 (16.70),
93 (22.90), 92 (13.50), 91 (20.80), 81 (41.70), 79 (50.00), 78 (52.10), 77 (74.60), 76
(79.20), 75 (60.40), 66 (16.70), 65 (33.30), 64 (49.00), 63 (51.00), 62 (41.70), 60
(77.90), 59 (100.00), 58 (25.00), 53 (46.90), 51 (41.70), 50 (61.50). Anal. Found: C,
35.38; H, 3.19; N, 13.66; S, 10.45. C9H10N3BrO2S requires: C, 35.64; H, 3.30; N,
13.86; S, 10.56.
5-Aryl-2-[(5-substituted-3-methoxy-2 hydroxy-benzylidene)-hydrazino]-
thiazoles (3a,b)
3-[(5-Substituted-3-methoxy-2-hydroxy benzy-lidene)amino]-4-oxo-imidazolidin-2-
thiones (4a,b)
9
A mixture of 2a,b (0.01 mol) with x-bromomethyl aryl ketones such as (4-
methylphenacyl bromide and 4-methoxy phenacyl bromide) and ethylchloroacetate
in presence of fused sodium acetate in methanol under reflux for 4 h, then cooled
and poured into water. The solid formed was filtered off, dried and purified by
recrystallization from suitable solvent to give 3 and 4.
123

Synthesis and characterization of thiazole
Table 4 IC50 (mg) values of
Compound
Tuinor type/cell line
MCF-7
tumor cell lines after 72 h
continuous exposure to test
compounds
HePG2
3a
3b
4a
4b
5a
5b
6a
6b
7a
16.20
Weak
14.50
39.40
12.00
Weak
38.90
34.90
Weak
21.70
Weak
6.90
36.30
9.90
IC50 is the concentration that
induces 50 % growth inhibition
compared with untreated control
cells
Weak
23.90
21.50
Weak
MCF-7 human breast carcinoma
cell line, HePG2 human
hepatocellular carcinoma cell
line
5-(p-Tolyl)-2-[(3-methoxy-2-hydroxybenzylidene)-hydrazino]-thiazoles (3a) as
yellow crystals, yield 69 % m.p. 190 °C. IR(KBr): 3,490–2,970 (br.OH), 3,289
(NH), 1,616 (C=N), 1,605, 1,583 (C=C), 1,215, 1,125, 1,093 (C–O)cm-1. 1H-NMR
(CDCl3): d 2.46 (s,3H,CH3), 3.89 (s,3H,OCH3), 6.97–7.75 (m,8H,Ar-HandH-
thiazole), 8.21 (s,1H,CH=N), 9.81 (s,1H,NH), 11.20 (s,1H,OH)ppm. MS: (m/z,
%):340 Mþþ1, 5.70), 339 (M?,21.90), 338 (M?-1,3.00), 323 (8.30), 322 (28.60),
321 (14.90), 226 (14.40), 225 (100), 224 (9.50), 204 (2.80), 208 (10.50), 207 (6.30),
191 (7.00), 190 (41.90), 189 (8.90), 188 (6.70), 176 (6.40), 175 (3.20), 174 (4.10),
166 (3.40), 165 (5.40), 164 (3.70),162 (3.90), 152 (8.60), 151 (10.80), 150 (42.20),
149 (36.60), 148 (36.90), 147 (22.90), 137 (13.20), 136 (10.70), 135 (27.60), 134
(24.90), 133 (12.60),131 (12.20), 122 (13.70),121 (16.40), 119 (11.70), 118 (9.70),
108 (19.80), 107 (15.10), 106 (25.20), 105 (19.20), 104 (11.10), 102 (13.90), 101
(11.20), 94 (10.30), 93 (16.50), 91 (16.00), 90 (10.00), 80 (13.20), 79 (17.20), 78
(21.30), 77 (69.80), 76 (36.90), 75 (12.10), 66 (14.30), 65 (36.30), 64 (14.30), 63
(25.10), 60 (47.50), 59 (18.90), 53 (20.70), 52 (40.90), 51 (40.30), 50 (22.00). Anal.
Found: C, 63.66; H, 4.97; N, 12.23; S, 9.35. C18H17N3O2S requires: C, 63.72; H,
5.01; N, 12.39; S, 9.44.
5-(p-Methoxyphenyl)-2-[(5-bromo-3-methoxy-2-hydroxybenzylidene)-hydra-
zino]-thiazoles (3b) as yellow crystals, yield 69 % m.p. 140 °C. IR (KBr):
3,480–2,951 (br.OH), 3,225, (NH), 1,618 (C=N), 1,605, 1,591 (C=C), 1,225, 1,093
(C–O)cm-1. 1HNMR (CDCl3): d 3.91–3.97 (s,6H,29OCH3), 6.91–7.68 (m,7H, Ar-
HandH-thiazole), 8.31 (s,1H,CH=N), 9.88 (s,1H,NH), 11.21 (s,1H,OH) ppm. MS:
(m/z, %): 435 (M??2,28.35),433 (M?,46.74), 418 (46.60), 416 (39.39), 354
(11.110), 353 (21.30), 343 (11.12), 341 (10.02), 310 (20.89), 308 (35.70), 306
20.05), 300 (6.31), 299 (16.29), 294 (8.27), 292 (14.26), 286 (28.00), 284 (27.74),
282 (16.77), 280 (26.98), 277 (28.35), 271 (19.60), 269 (53.92), 228 (51.85), 226
(11.80), 224 (19.87), 220 (24.84), 215 (43.07), 213 (42.81), 207 (16.93), 206 (100),
204 (45.12), 199 (27.28), 197 (12.17), 191 (50.60), 184 (20.60), 177 (23.44), 172
(10.72), 170 (10.72), 164 (74.75), 161 (15.41), 159 (18.40), 150 (18.07), 149
(57.91), 148 (23.81), 143 (19.22), 135 (48.25), 134 (24.99), 133 (20.56), 121
123

M. H. Sherif et al.
(27.69), 120 (13.65), 119 (12.08), 107 (12.024), 96 (27.75), 94 (48.38), 91 (14.34),
90 (13.37), 89 (12.07), 79 (24.00), 78 (17.64), 77 (35.87), 76 (18.73), 65 (9.13), 64
(13.53), 63 (34.12), 62 (20.14), 53 (11.21), 51 (20.92), 50 (20.22). Anal. Found: C,
49.66; H, 3.59; N, 9.62; S, 7.22. C18H16N3BrO3S requires: C, 49.88; H, 3.69; N,
9.70; S, 7.39.
3-[3-Methoxy-2-hydroxybenzylidene)amino]-4-oxo-imidazolidin-2-thione (4a)
as pale yellow crystals, yield 73 % m.p. 320 °C. IR (KBr): 3,520–2,947 (br.OH),
3,417 (NH), 1,708 (C=O), 1,635 (C=N), 1,249, 1,087 (C–O)cm-1
.
1H-
NMR(DMSO-d3):
d 3.20 (s,2H,NHCH2CO), 3.95 (s,3H,OCH3), 7.12–7.60
(m,3H,Ar–H), 8.21 (s,1H,CH0=N), 10.20 (s,1H,NH), 11.32 (s,1H,OH)ppm. MS:
(m/z, %): 266 (M??1,10.5), 265 (M?,76.20), 264 (M?-1, 55.30), 249 (15.80), 248
(100), 247 (67.60), 235 (2.5), 234 (2.00), 222 (8.30), 221 (6.10), 218 (2.60), 205
(1.60), 194 (1.80), 193 (1.70), 192 (2.00), 176 (2.50), 175 (1.80), 174 (4.90), 165
(2.20), 163 (1.70), 162 (2.60), 151 (5.60), 150 (26.30), 149 (21.50), 148 (12.00), 136
(6.90), 135 (16.80), 134 (18.20), 132 (9.20), 130 (6.90), 122 (10.20), 121 (14.10),
120 (10.00), 119 (9.60), 117 (18.90), 116 (16.40), 108 (18.10), 107 (16.00), 106
(23.30), 105 (10.70), 93 (15.50), 92 (14.20), 91 (7.30), 89 (5.20), 79 (14.10), 78
(18.30), 77 (16.10),76 (12.80), 66 (8.30), 65 (34.90), 64 (18.20), 63 (21.00), 53
(16.70), 52 (28.30), 51 (31.30), 50 (17.40), 90 (13.37), 89 (12.07), 79 (24.00), 78
(17.64), 77 (35.87), 76 (18.73). Anal. Found: C, 49.62; H, 4.03; N, 15.58; S, 11.97.
C11H11N3O3S requires: C, 49.81; H, 4.15; N, 15.85; S, 12.07.
3-[(5-Bromo-3-methoxy-2-hydroxybenzylidene)-amino]-4-oxo-imidazolidin-2-
thione (4b) as yellow crystals, yield 71 % m.p. 310 °C. IR (KBr): 3,520–2,950
(br.OH), 3,429 (NH), 1,716 (C=O), 1,635 (C=N), 1 605, 1,589 (C=C), 1,319 (C=S),
.
1,211, 1,110 (C–O)cm-1 1H-NMR (CDCl3): d 3.21 (s,2H,NHCH2CO), 3.93
(s,3H,OCH3), 7.23 (s,1H,Ar–H), 7.52 (s,1H,Ar–H), 8.61 (s,1H,CH=N), 9.90
(s,1H,NH), 12.05 (s,1H,OH)ppm. MS: (m/z, %): 345 (M??2,43.30), 344
(M??1,60.90), 343 (M?,60.00), 342 (M?-1,50.00), 339(16.70), 328 (66.70), 327
(30.00), 326 (76.70), 264 (23.30), 172 (16.70), 154 (6.70), 148 (6.70), 135 (6.70),
123 (20.00), 120 (40.00), 119 (36.70), 118 (26.70), 117 (53.30), 116 (33.30), 105
(3.30), 104 (33.30), 103 (6.70), 102 (33.30), 96 (26.70), 89 (46.70), 88 (16.70), 84
(26.70), 82 (40.00), 81 (20.00), 80 (10.00), 78 (10.00), 76 (100), 68 (43.30), 64
(33.30), 60 (26.70), 59 (20.00), 58 (63.30), 53 (6.70), 50 (20.00). Anal. Found: C,
38.26; H, 2.78; N, 12.09; S, 9.13. C11H10N3BrO3S requires: C, 38.48; H, 2.91; N,
12.24; S, 9.33.
5-Aryl-2-[(5-substituted-3-methoxy-2-acetoxy-benylidene)-
acetylhydrazino]thiazoles (5a,b)
3-[(5-Substituted-3-methoxy-2-acetoxybenzylidene) amino]-4-oxo-1-
acetylimidazolidin-2-thiones (6a,b)
A solution of 3 and 4 (0.01 mol) in acetic anhydride (20 ml) was heated under
reflux for 2 h, then cooled and poured into ice-water. The solid obtained was filtered
off, washed with water, dried and purified by recrystallization with ethanol to give 5
and 6.
123

Synthesis and characterization of thiazole
5-(p-Tolyl)-2-[(3-methoxy-2-acetoxybenzylidine)-acetylhydrazine]thiazole (5a)
as pale yellow crystals, yield 68 %, m.p. 80 °C. I.R(KBr): 1,758 (C=O), 1,715
(C=O), 1,630 (C=N), 1,605, 1,585 (C=C), 1,215, 1,085 (C–O)cm-1 1H-NMR
.
(CDCl3): d 2.30 (s,3H,CH3), 2.43 (s,3H,COCH3), 2.60 (s,3H,OCOCH3), 3.87
(s,3H,OCH3), 7.03–7.76 (m,8H,Ar-HandH-thiazole), 9.21 (s,1H,CH=N) ppm. MS:
(m/z, %): 424 (M??1,12.70), 423 (M?,8.90), 422 (M?-1,22.80), 382 (10.10), 381
(30.40), 380 (27.80), 350 (6.30), 349 (15.20), 340 (15.20), 340 (15.20), 339 (20.30),
338 (17.70), 323 (26.60), 322 (100), 320 (19.00), 308 (24.00), 307 (20.30), 290
(15.20), 289 (26.60), 288 (17.70), 280 (11.40), 279 (20.30), 276 (13.90), 266
(26.60), 265 (51.90), 264 (21.50), 250 (20.80), 249 (24.10), 248 (41.80), 247
(58.20), 233 (11.10), 232 (11.40), 230 (12.70), 217 (15.60), 216 (12.70), 208
(20.30), 205 (31.60), 204 (10.10), 195 (13.90), 194 (11.40), 193 (15.20), 192
(17.70), 191 (16.50), 190 (89.90), 189 (88.6), 188 (26.60), 187 (64.60), 179 (16.50),
178 (11.40), 177 (15.50), 175 (20.30), 167 (13.90), 166 (13.90), 162 (13.90), 161
(15.20), 159 (24.10), 151 (34.20), 150 (31.60), 149 (54.40), 148 (64.40), 147
(44.30), 146 (38.00), 132 (15.20), 131 (20.30), 123 (11.40), 122 (31.60), 121
(20.30), 120 (19.00), 119 (40.50), 118 (19.00), 116 (22.80), 108 (19.00), 107
(30.40), 105 (13.90), 103 (15.20), 102 (27.80), 97 (19.00), 96 (17.70), 95 (20.30), 93
(24.10), 92 (27.80), 91 (34.20), 90 (11.40), 80 (25.30), 79 (34.20), 77 (46.80), 76
(27.80), 66 (20.30), 65 (26.60), 64 (20.30), 63 (27.80), 61 (20.30), 60 (55.70), 59
(32.90), 57 (30.40), 52 (27.80), 51 (49.40), 50 (32.90). Anal. Found: C, 62.26; H,
4.83; N, 9.78; S, 7.49. C22H21N3O4S requires: C, 62.41; H, 4.96; N, 9.93; S, 7.56.
5-(p-Methoxyphenyl)-2-[(5-bromo-3-methoxy-2-acetoxybenzylidine)-acetylhy-
drazino]thiazole (5b) as pale yellow crystals, yield 67 %, m.p. 85 °C. I.R (KBr):
1,753 (C=O), 1,716 (C=O), 1,631 (C=N), 1,606, 1,589 (C=C), 1,212, 1,175, 1,083
(C–O)cm-1
3.95–3.97
.
1HNMR (CDCl3): d 2.35 (s,3H,COCH3), 2.55 (s,3H,OCOCH3),
(s,6H,2O9CH3), 7.03–7.61 (m,7H,Ar-HandH-thiazole),8.36
(s,1H,CH = N) ppm. MS:(m/z, %): 519 (M??2,100), 518 (M??1,30.20), 517
(M?,76.20), 512 (25.11), 498 (43.12), 496 (34.52), 478 (13.28), 476 (89.14), 443
(25.29), 434 (55.50), 418 (82.55), 416 (92.31), 384 (14.80), 361 (14.58), 353
(32.79), 343 (16.91), 341 (12.25), 336 (20.17), 328 (23.27), 326 (18.14), 310
(15.42), 309 (56.61), 307 (67.71), 305 (36.97), 294 (10.23), 291 (17.00), 288
(28.91), 286 (35.46), 284 (36.27), 264 (11.84), 263 (35.07), 251 (10.87), 249
(15.98), 248 (57.12), 232 (14.94), 231 (13.50), 230 (34.69), 229 (96.76), 227
(71.12), 220 (24.12), 215 (25.71), 213 (23.55), 206 (87.98), 204 (40.63), 202
(11.62), 200 (16.22), 194 (14.06), 191 (30.44), 189 (16.34), 186 (10.93), 184
(11.27), 164 (39.79), 161 (7.84), 150 (7.16), 149 (21.92), 135 (22.79), 134 (9.17),
119 (6.34), 104 (5.82), 91 (7.25), 90 (7.28), 77 (12.78), 76 (12.43), 75 (13.09), 63
(9.51), 62 (5.65), 50 (4.61), 43 (76.85). Anal. Found: C, 51.03; H, 3.68; N, 8.07; S,
6.13. C22H20N3BrO5S requires: C, 51.06; H, 3.87; N, 8.12; S, 6.19.
1-Acetyl-3-[(3-methoxy-2-acetoxybenzylidene) amino]-4-oxo-imidazolidin-2-
thione (6a) as pale yellow crystals, yield 65 %, m.p. 260 °C. IR(KBr): 1,762,
1,724, 1,695 (C=O), 1,625 (C=N), 1,608, 1,585 (C=C), 1,328 (C=S), 1,215, 1,095
.
(C–O)cm-1 1HNMR(DMSO-d6): d 2.34 (s,3H,COCH3), 2.56 (s,3H,OCOCH3),
3.25 (s,2H,NCH2CO), 3.91 (s, 3H, OCH3),7.12–7.58(m,3H,Ar–H), 8.35
(s,1H,CH=N) ppm. MS: (m/z, %): 350 (M??1,2.50), 3 49 (M?,7.90), 348 (M?-
123

M. H. Sherif et al.
1,5.40), 307 (22.10), 306 (9 0.30), 290 (6.80), 289 (6.20), 267 (5.70), 266 (11. 3 0),
265 (75.40), 264 (46.50), 263 (11.00), 249 (15. 30), 248 (100), 247 (11.90), 236
(7.60), 235 (6.20), 223 (11.80), 222 (9.60), 194 (5.70), 193 (5.40), 192 (4.20), 177
(5.10), 165 (2.30), 159 (23.5 0), 158 (20.70), 151 (7.40), 150 (27.80), 149 (27.50),
148 (24.10), 135 (12.50), 134 (10.20), 132 (9.10), 131 (7.90), 122 (15.00), 121
(12.70), 119 (17.60), 118 (10.50), 117 (25.50), 116 (20.10), 107 (9.90), 106 (17.00),
104 (5.70), 93 (12.20), 92 (10. 80), 91 (6 0.5 0), 78 (8.60), 77 (12.70), 76 (11. 90),
73 (14.70), 6 5 (19.50), 64 (16.70), 63 (14.40), 59 (10.20), 53 (1 0.80), 52 (11.30),
51 (16.40), 50 (11.60). Anal. Found: C, 51.48; H, 4.13; N, 11.96; S, 9.02.
C15H15N3O5S requires: C, 51.57; H, 4.30; N, 12.03; S, 9.17.
1-Acetyl-[(5-bromo-3-methoxy-2-acetoxybenzylidene) amino]-4-oxo-imidazoli-
din-2-thione (6b) as pale yellow crystals, yield 63 %, m.p. 230 °C. IR(KBr): 1,766,
1,732, 1,699 (C=O), 1,651 (C=N), 1,608, 1,583 (C=C), 1,319 (C=S), 1,180, 1,010
(C–O)cm-1. 1HNMR(DMSO-d6): d2.35 (s,3H,COCH3), 2.49 (s,3H,OCOCH3), 3.23
(s,2H,NCH2CO), 3.95 (s,3H, OCH3), 7.33 (s,1H,Ar–H), 7.63 (s,1H,Ar–H), 8.33
(s,1H,CH=N) ppm. MS:(m/z, %): 429 (M??2, 1.30), 427 (M?,1.70), 388 (22.00),
387 (58.50), 386 (34.10), 385 (56.10), 384 (51.20), 345 (31.70), 344 (63.40), 343
(65.90), 342 (75.60), 328 (65.90), 327 (61.00), 326 (70.70), 325 (100), 314 (22.00),
308 (22.00), 307 (26.80), 306 (29.30), 275 (9.80), 274 (17.10), 265 (29.30), 264
(31.70), 246 (12.20), 245 (22.00), 227 (36.60), 219 (14.60), 218 (17.10), 214
(17.10), 213 (22.00), 203 (14.60), 202 (29.30), 201 (29.30), 199 (29.30), 198
(29.30), 190 (22.00), 189 (11.50), 188 (14.60), 187 (14.60), 185 (19.50), 173
(12.60), 159 (43.90), 158 (9.80), 150 (7.30), 147 (2 4.40), 146 (19.50), 142 (63.40),
135 (36.60), 133 (24.40), 122 (17.10), 120 (29.30), 119 (22.00), 118 (17.10), 117
(58.60), 116 (29.30), 114 (43.90), 113 (43.90), 112 (17.10), 107 (24.40), 106
(19.50), 102 (31.70), 95 (24.40), 93 (41.50), 92 (9.50), 91 (26.8 0), 89 (14.60), 88
(19.50), 87 (26.80), 82 (36.60), 8 1 (24.40), 79 (41.50), 77 (12.20), 75 (12.20), 74
(22.00), 72 (22.00), 71 (22.00), 65 (26.80), 64 (31.70), 63 (63.40), 62 (41.50), 61
(26.80), 59 (73.20), 54 (41.50), 53 (39.00), 51 (22.00), 50 (19.50). Anal. Found: C,
42.01; H, 3.05; N, 9.63; S, 7.22. C15 H14 N3BrO5S requires: C, 42.15; H, 3.28; N,
9.84; S, 7. 49.
1,5-Dicetyl-3-[(5-substituted-3-methoxy-2-acetoxy-benzylidene)-amino]-4-oxo-
imidazolidin-2-thione (7a,b)
A mixture of 4 (0.01 mol) and fused sodium acetate (0.03 mol) in acetic anhydride
(25 ml) was heated under reflux for 3 h, then cooled and poured into ice-diluted
hydrochloric acid. The solid obtained was filtered off, washed with water, dried and
purified by recrystallization with ethanol to 7.
1,5-Dicetyl-3-[(3-methoxy-2-acetoxybenzylidene)amino]-4-oxo-imidazolidin-2-
thione (7a) as pale yellow crystals, yield 62 %, m.p. 180 °C. IR (KBr): 1,763, 1,725,
1,698 (C=O), 1,625 (C=N), 1,603, 1,588 (C=C), 1,325 (C=S), 1,225, 1,125,
1,089(C–O) cm-1. 1HNMR (CDCl3): d 2.21 (s,3H,COCH3), 2. 43 (s,3H,OCOCH3),
2.51 (s,3H,OCH3), 5.67 (s, 1H,NCH(CO)2), 7.31 (s,1H,Ar–H), 7.61(s,1H,Ar–H),
8.46 (s,1H,CH=N), 3.93 (s,3H,OCH3) ppm. MS: (m/z, %): 391 (M?,21.30), 390
(M?-1,15.40), 363 (24.30), 362 (10.30), 349 (32.40), 348(12.50), 322 (11.80), 321
123

Synthesis and characterization of thiazole
(61.80), 320 (41.20), 308 (12.50), 307 (96.90), 306 (61.00), 305 (61.20), 304
(16.90), 291 (22.80), 290 (71.30), 289 (57.40), 288 (10.30), 280 (22.10), 279 (100),
278 (50.00), 277 (14.00), 265 (49.30), 264 (22.40), 250 (10.30), 249 (19.10), 248
(56.60), 247 (30.90), 236 (24.30), 235 (18.40), 223 (14.00), 219 (16.20), 218
(10.30), 213 (13.20), 201 (18.40), 200 (16.90), 195 (10.30), 194 (16.20), 193
(14.70), 192 (19.40), 191 (16.20), 177 (21.30), 176 (14.00), 175 (10.30), 170
(14.00), 164 (19.10), 163 (13.20), 162 (23.50), 161 (11.80), 152 (15.40), 151
(19.10), 150 (81.60), 149 (73.50), 148 (39.70), 136 (13.20), 135 (36.60), 134
(16.20), 133 (17.60), 132 (25.00), 131 (28.70), 130 (22.10), 122 (27.20), 121
(25.70), 120 (26.50), 119 (24.30), 118 (24.30), 117 (27.20), 116 (50.00), 109
(12.50), 107 (31.60), 106 (41.90), 105 (24.30), 104 (23.40), 95 (16.90), 93 (27.20),
92 (48.50), 91 (25.00), 90 (25.70), 88 (32.40), 87 (14.00), 80 (16.90), 79 (26.50), 78
(22. 80), 77 (37.50), 76 (19.90), 75 (15.40), 73 (15.40), 69 (30.10), 67 (26.50), 65
(39.70), 64 (37.50), 63 (33.10), 62 (25.70), 57 (63.20), 56 (22.10), 55 (28.70), 52
(22.80), 51 (35.30), 50 (17.60). Anal. Found: C, 52.07; H,4.22; N, 10.56; S, 8.03.
C17H17 N3O6S requires: C, 52.17; H, 4.35; N, 10.74; S, 8. 17.
1,5-Diacetyl-3-[(5-bromo-3-methoxy-2-acetoxy-benzylidene)amino]-4-oxo-imi-
dazolidin-2-thione (7b) as yellow crystals, yield 61 %, m.p. 140 °C. IR(KBr):
1,162, 1,722, 1,698 (C=O), 1,629 (C=N), 1,603, 1,592 (C=C), 1,325 (C=S), 1,215,
. d 2.21 (s,3H,COCH3), 2.41
1,317, 1,081 (C–O)cm-1 1HNMR(CDCl3):
(s,3H,COCH3), 2.56 (s,3H,OCOCH3), 3.96 (s,3H,OCH3), 5.62 (s,1H,NCH(CO)2),
7.31 (s, 1H,Ar–H), 7.61 (s,1H,Ar-H), 8.41 (s,1H,CH=N) ppm. MS: (m/z, %):
471(M??2,13.10), 469 (M?,13.20), 468 (M?-1,10.20), 444 (23.20), 443 (19.20),
442 (12.10), 326 (9.10), 310 (22.20), 309 (13.10), 308 (37.40), 307 (20.20), 306
(19.20), 305 (13.10), 280 (19.20), 279 (17.20), 278 (16.20), 277 (13.10), 265 (6.10),
231 (15.20), 230 (79.80), 229 (51.50), 228 (63.60), 227 (72.70), 216 (16.20), 215
(13.10), 214 (14.10), 213 (18.20), 202 (39.40), 201 (40.40), 200 (38.40), 199
(38.40), 198 (20.20), 197 (13.10), 187 (19.20), 186 (12.10), 171 (20.20), 169 (7.10),
160 (12.10), 159 (18.20), 158 (13.10), 157 (15.20), 150 (12.10), 149 (13.10), 142
(13.10), 141 (27.30), 135 (14.10), 134 (16.20), 131 (14.10), 121 (20.20), 118
(15.20), 116 (13.10), 114 (14.10), 106 (17.20), 105 (13.10), 101 (11.10), 94 (13.10),
93 (14.10), 92 (15.20), 91 (31.30), 90 (19.20), 82 (25.30), 81 (2 3.20), 80 (19.20), 79
(34.30), 78 (32.30), 77 (32.30), 76 (21.20), 75 (34.30), 66 (18.20), 65 (32.30), 6 4
(25.30), 63 (100), 62 (52.50), 61 (34.30), 60 (3 8. 40), 53 (31.30), 51(41.40), 50
(63.40). Anal. Found: C, 43.29; H, 3.21; N, 8.72; S, 6.66. C17H16 N3 BrO6 S
requires: C, 43.49; H, 3.41; N, 8.95; S, 6.82.
Acknowledgment The authors acknowledge the regional center for mycology and biotechnology for
research, Al-Azhar University, for evaluation of cytotoxicity against MCF-7 and HePG2 cell lines.
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