Synthesis and Cytotoxic Activity against K562 and MCF7 Cell Lines of Some N -(5-Arylidene-4-oxo-2-thioxothiazolidin-3-yl)-2-((4-oxo-3-phenyl-3,4-dihydroquinazoline-2-yl)thio)acetamide Compounds

Article abstract of DOI:10.1155/2019/1492316

Ethyl 2-((4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)acetate (3) which was synthesized starting from anthranilic acid (1) via 2-thioxo-3-phenylquinazolin-4(3H)-one (2) reacted with hydrazine hydrate to afford 2-((4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)acetohydrazide (4). Reaction of (4) with thiocarbonyl-bis-thioglycolic acid gave a new compound name N-(4-oxo-2-thioxothiazolidin-3-yl)-2-((4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)acetamide (5). Knoevenagel condensation of (5) with appropriate aldehydes gave fourteen (Z)-N-(5-arylidene-4-oxo-2-thioxothiazolidin-3-yl)-2-((4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)acetamide compounds (6a-o) with moderate yield. The chemical structure of the compounds was elucidated on the basis of IR, ¹H-NMR, ¹³C-NMR, and HR-MS spectral data. The 5-arylidene-2-thioxothiazolidinone compounds exhibited mild-to-moderate cytotoxic activity against both K562 (chronic myelogenous leukemia) cells and MCF7 (breast cancer) cells.

Full text of DOI:10.1155/2019/1492316

Hindawi
Journal of Chemistry
Volume 2019, Article ID 1492316, 8 pages
https://doi.org/10.1155/2019/1492316
Research Article
Synthesis and Cytotoxic Activity against K562 and MCF7 Cell
Lines of Some N-(5-Arylidene-4-oxo-2-thioxothiazolidin-3-yl)-2-
((4-oxo-3-phenyl-3,4-dihydroquinazoline-2-yl)thio)
acetamide Compounds
Cong T. Nguyen ,1 Quang T. Nguyen,1 Phuc H. Dao,1 Thuan L. Nguyen,1
Phuong T. Nguyen,2 and Hung H. Nguyen3
1Department of Chemistry, Ho Chi Minh City University of Education, Ho Chi Minh City 72711, Vietnam
2Nguyen Tat #anh Institute of Hi-Technology, Nguyen Tat #anh University, Ho Chi Minh City 72820, Vietnam
3Faculty of Biotechnology, Nguyen Tat #anh University, Ho Chi Minh City 72820, Vietnam
Correspondence should be addressed to Cong T. Nguyen; congnt@hcmup.edu.vn
Received 29 June 2019; Accepted 22 August 2019; Published 10 September 2019
Academic Editor: Henryk Kozlowski
Copyright © 2019 Cong T. Nguyen et al. )is is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is
properly cited.
Ethyl 2-((4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)acetate (3) which was synthesized starting from anthranilic acid (1) via
2-thioxo-3-phenylquinazolin-4(3H)-one (2) reacted with hydrazine hydrate to afford 2-((4-oxo-3-phenyl-3,4-dihydroquinazolin-
2-yl)thio)acetohydrazide (4). Reaction of (4) with thiocarbonyl-bis-thioglycolic acid gave a new compound name N-(4-oxo-2-
thioxothiazolidin-3-yl)-2-((4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)acetamide (5). Knoevenagel condensation of (5)
with appropriate aldehydes gave fourteen (Z)-N-(5-arylidene-4-oxo-2-thioxothiazolidin-3-yl)-2-((4-oxo-3-phenyl-3,4-dihy-
droquinazolin-2-yl)thio)acetamide compounds (6a–o) with moderate yield. )e chemical structure of the compounds was
elucidated on the basis of IR, 1H-NMR, 13C-NMR, and HR-MS spectral data. )e 5-arylidene-2-thioxothiazolidinone compounds
exhibited mild-to-moderate cytotoxic activity against both K562 (chronic myelogenous leukemia) cells and MCF7 (breast
cancer) cells.
[30], glycogen synthase kinase-3 (GSK-3) [31, 32], 17β-
hydroxysteroid dehydrogenase type 3 [33], and histone
acetyltransferases (HATs) [34]. Specifically, the 5-aryli-
dene-2-thioxothiazolidine-4-one moiety is reported to
possess anticonvulsant [35], antimicrobial [36], antidia-
betic [37], antitumor [38–40], and anticancer activities
[41–44]. )e aforementioned compounds have inspired the
idea of synthesizing hybrid derivatives where moieties of
quinazolin-4-one and 2-thioxothiazolidin-4-one could be
incorporated with each other to be an organic molecule
with more effective anticancer activity. )erefore, we report
here the synthesis of N-(4-oxo-2-thioxothiazolidin-3-yl)-2-
((4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)acet-
amide and 5-arylidene derivatives of this compound as
1. Introduction
Quinazolinones were considered to be a scaffold with po-
tential biological activities. Besides possessing a variety of
biological effects including antimicrobial [1–6], anticonvul-
sant [7, 8], and antihistamine [9, 10] activities, compounds
containing quinazolin-4-one nucleus also showed promising
anticancer potency [11–20]. Along with that, 5-arylidene-2-
thioxothiazolidine-4-one compounds are an important class
of compounds with a wide range of pharmaceutical prop-
erties. )e 5-arylidene-2-thioxothiazolidine-4-one derivatives
have been shown to inhibit aldose reductase [21–24], hepatitis
C virus (HCV) [25, 26], human immunodeficiency virus
(HIV) [27–29], JNK-stimulating phosphatase-1 (JSP-1)

2
Journal of Chemistry
well as evaluate their toxicity on some cell lines including
K562 (chronic myelogenous leukemia) cells and MCF7
(breast cancer) cells.
pure product 3. Yield: 65.0%; mp: 106–107°C (lit. [45]:
105–107°C); IR (], cm− 1): 3059 (C-H aromatic), 2976, 2906
(C-H aliphatic), 1732 (C�O ester), 1680 (C�O ketone), 1607,
1
1598, and 1468 (C�N, C�C aromatic); H-NMR (δ, ppm):
3
3
8.09 (1H, d, J � 8.0 Hz, Ar-H), 7.84 (1H, d, J � 7.5 Hz, Ar-
H), 7.61–7.48 (7H, m, Ar-H), 4.15 (2H, q, 3J � 7.0 Hz,
-CH2CH3), 3.99 (2H, s, -SCH2-), and 1.23 (3H, t, 3J � 7.0 Hz,
CH3) (see S2a and S2b from Supporting Information).
2. Materials and Methods
All starting materials were purchased from Acros and used
without purification. Melting points were measured in
open capillary tubes on a Gallenkamp melting point
apparatus.
3.3. Synthesis of 2-((4-Oxo-3-phenyl-3,4-dihydroquinazolin-
2-yl)thio)acetohydrazide (4). To a solution of ester 3 (6.8 g,
20 mmol) in ethanol (50 mL), excess of hydrazine hydrate
80% (1.5 g, 30 mmol) was added. )e reaction mixture
was refluxed on a water bath for 10 h. After cooling, the
solid separated was filtered and recrystallized from eth-
anol to give crystals of compound 4. Yield: 68%; mp:
194–196°C (lit. [15]: 195–196°C); IR (], cm− 1): 3279
(N-H), 3059 (C-H aromatic), 2916 (C-H aliphatic), 1690,
1659 (C�O), 1605, 1547, and 1466 (C�N, C�C aromatic);
1H-NMR (δ, ppm): 9.33 ppm (1H, s, NH), 8.09 (1H, d,
)e structure of all compounds was confirmed by their
1
IR, H-NMR, 13C-NMR, and HR-MS spectral data. IR
spectra (], cm− 1) were recorded on a FTIR-8400S-SHI-
MADZU spectrometer using KBr pellets. )e NMR
spectra were recorded on a Bruker Avance III spec-
trometer (500 MHz for 1H-NMR and 125 MHz for
13C-NMR) using residual solvent DMSO-d6 signals (δH
2.50, δC 39.52) as internal references. )e spin-spin
coupling constants (J) are given in Hz. Peak multiplicity is
reported as s (singlet), d (doublet), dd (doublet-doublet),
t (triplet), q (quartet), and m (multiplet). )e HR-ESI-MS
spectra were recorded on a Bruker micrOTOF-Q 10187
spectrometer.
3
3
3J � 8.0 Hz, Ar-H), 7.86 (1H, dd, J1 � J2 � 8.0 Hz, Ar-H),
3
7.63 (1H, d, J � 8.0 Hz, Ar-H), 7.59–7.62 (3H, m, Ar-H),
7.48–7.51 (3H, m, Ar-H), 4.28 ppm (2H, br, -NH2-), and
3.86 ppm (2H, s, -SCH2-) (see S3a and S3b from Sup-
porting Information).
)e cytotoxic activity of 6a–o compounds was tested on
K562 (chronic myelogenous leukemia) and MCF7 (breast
cancer) cell lines using the MTT assay.
3. Experimental
3.4. Synthesis of N-(4-Oxo-2-thioxothiazolidin-3-yl)-2-((4-
oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)acetamide (5).
A mixture of compound 4 (1.63 g, 5 mmol) and thio-
carbonyl-bis-thioglycolic acid (1.13 g, 5 mmol) in absolute
ethanol (15 mL) was refluxed for 8 h. After cooling, the
resulting solid was filtered, dried, and recrystallized from
AcOH to give yellowish powder compound 5. Yield: 55.0%;
mp: 237–238°C. IR (], cm− 1): 3202 (N-H), 3001 (C-H aro-
matic), 1759, 1690 (C�O), 1551, 1466 (C�C aromatic, C�N),
)e synthesis of the target compounds is carried out as
outlined in Scheme 1.
3.1. Synthesis of 2-Mercapto-3-phenylquinazolin-4-one (2).
To the solution of anthranilic acid 1 (13.7 g, 0.1 mol) and
phenyl isothiocyanate (13.5 g, 0.1 mol) in absolute ethanol
(200 mL), triethylamine (3.0 mL) was added and the reaction
mixture was refluxed for 4.0 h. After cooling to room
temperature, the reaction mixture was poured into water
and then filtered. )e precipitate was recrystallized from a
mixture of DMF and water and washed with cold ethanol to
give crystals. Yield: 80.0%; mp: 295–297°C (lit. [2, 5] 296–
298°C); IR (], cm− 1): 3217, 3134 (N-H, S-H), 3028 (C-H
aromatic), 1659 (C�O), 1618, 1524, and 1485 (C�N, C�C
aromatic); 1H-NMR (δ, ppm): 13.05 (1H, s, SH), 7.96 (1H, d,
1
and 1250 (-N-C�S); H-NMR (δ, ppm): 11.31 (1H, s, NH),
3
8.09 (1H, d, 3J � 8.0 Hz, Ar-H), 7.86 (1H, dd, 3J1 � J2 � 8.0 Hz,
Ar-H), 7.76 (1H, d, 3J � 8.0 Hz, Ar-H), 7.62–7.60 (3H, m, Ar-
H), 7.51–7.48 (3H, m, Ar-H), 4.41 ppm (2H, m, -CH2-
thiazolidine ring), and 4.13 (2H, m, -S-CH2-CONH); 13C-
NMR (δ, ppm): 200.1 (C�S), 170.5, 166.0, 161.2 (C�O),
156.5, 147.6, 136.2, 135.2, 130.5, 130.1, 129.9, 127.0, 126.9,
126.6, 120.0 (CAr), 34.5 (-SCH2-), and 33.8 (-CH2- thiazo-
lidine ring); HR-ESI-MS m/z 443.0367 (M + H)+ calcd. for
(C19H15N4O3S3) 443.0306 (see S4a–S4d from Supporting
Information).
3J � 8.0 Hz, Ar-H), 7.80 (1H, dd, J1 � J2 � 8.0 Hz, Ar-H),
3
3
7.50–7.40 (4H, m, Ar-H), 7.36 (1H, dd, 3J1 � J2 � 7.5 Hz, Ar-
3
H), and 7.29 (2H, d, 3J � 7.5 Hz, Ar-H) (see S1a and S1b from
Supporting Information).
3.5. General Procedure for Synthesis of N-(5-Arylidene-4-oxo-
2-thioxothiazolidin-3-yl)-2-((4-oxo-3-phenyl-3,4-dihydroquinazolin-
2-yl)sulfanyl) acetamides (6a–o). To a mixture of compound
5 (0.442 g, 1 mmol) and CH3COONa (0.082 g, 1 mmol) in
glacial acetic acid (15 mL), 1 mmol of appropriate aldehyde
was added and the solution was refluxed for 5 h. After
cooling to room temperature, the reaction mixture was
poured into ice-cold water and filtered. )e precipitate was
recrystallized from an appropriate solvent to give 6a–o
compounds, respectively.
3.2. Synthesis of Ethyl 2-((4-oxo-3-phenyl-3,4-dihydroquinazolin-
2-yl)thio)acetate(3). An equimolar mixture of 2-mercapto-3-
phenylquinazolin-4-one (2) (5.08 g, 20 mmol) and anhy-
drous potassium carbonate (2.76 g, 20 mmol) in dry DMF
(30 mL) was stirred for 30 minutes, and then, ethyl chlor-
oacetate (2.45 g, 20 mmol) was added. )e reaction mixture
was refluxed for 5 h then cooled to room temperature and
poured into ice-cold water. )e white precipitate was filtered
off and purified by crystallization from ethanol to afford

Journal of Chemistry
3
O
N
O
N
COOH
C6H5
SH
C6H5
S
ClCH2CO2C2H5
C6H5NCS
N
N
OC2H5
NH2
(1)
(2)
(3)
O
NH2NH2
SCH2COOH
SCH2COOH
O
O
O
S
C
C6H5
S
C6H5
S
C6H5
N
N
N
O
S
O
H
ArCHO
H
N
N
N
O
N
N
N
N
S
O
Ar
O
NH
S
H2N
S
S
(6a-o)
(5)
(4)
Ar = 4-(CH3)2NC6H4 (6a), 4-BrC6H4 (6b), 4-ClC6H4 (6c), 4-FC6H4 (6d), 2-FC6H4 (6e), 4-CH3OC6H4 (6f), 4-HOC6H4 (6g), 3-HOC6H4 (6h),
C6H5 (6i), 4-O2NC6H4 (6j), 3-O2NC6H4 (6k), 2-O2NC6H4 (6l), 3,4-(OCH2O)C6H3 (6m), 3-CH3O-4-HOC6H3 (6n), C6H5CH=CH (6o)
Scheme 1: Synthetic route for the preparation of the target compounds. Ar � 4-(CH3)2NC6H4 (6a), 4-BrC6H4 (6b), 4-ClC6H4 (6c), 4-FC6H4
(6d), 2-FC6H4 (6e), 4-CH3OC6H4 (6f), 4-HOC6H4 (6g), 3-HOC6H4 (6h), C6H5 (6i), 4-O2NC6H4 (6j), 3-O2NC6H4(6k), 2-O2NC6H4 (6l), 3,
4-(OCH2O)C6H3 (6m), 3-CH3O-4-HOC6H3 (6n), and C6H5CH � CH (6o).
3
3.5.1. N-(5-(4-Dimethylamino)benzylidene)-4-oxo-2-
thioxothiazolidin-3-yl)-2-((4-oxo-3-phenyl-3,4-dihydroquinazolin-
2-yl)thio)acetamide (6a). Yield: 59.0%; mp: 268–269°C; IR
(], cm− 1): 3237 (N-H), 2918 (Csp3-H), 1734, 1686 (C�O), 1584,
(1H, s, NH), 8.10 (1H, d, J � 7.0 Hz, Ar-H), 7.93 (1H, s,
3
3
–CH � ), 7.89 (1H, dd, J1 � J2 � 8.0 Hz, Ar-H), 7.79 (1H, d,
3J � 8.0 Hz, Ar-H), 7.72 (2H, d, 3J � 8.5 Hz, Ar-H), 7.64 (2H, d,
3J � 9.0 Hz, Ar-H), 7.63–7.60 (3H, m, Ar-H), 7.53–7.48 (3H,
m, Ar-H), and 4.17 (2H, m, -CH2-); 13C-NMR (δ, ppm): 188.7
(C�S), 167.3, 163.2, 161.1, (C�O), 158.8, 146.7, 137.4, 135.3,
135.0, 133.4, 131.8, 131.5, 130.7, 130.1, 129.8, 129.1, 127.8,
126.9, 125.4, 120.6 and 119.9 (CAr), and 33.6 (-CH2-); HR-
ESI-MS m/z 565.0236 (M + H)+ calcd. for (C26H18ClN4O3S3)
565.0230 (see S7a–S7d from Supporting Information).
1
1553, 1526 (C�N, C�C), and 1254 (-N-C�S); H-NMR (δ,
ppm): 11.44 (1H, s, NH), 8.10 (1H, d, 3J � 8.0 Hz, Ar-H), 7.88
3
3
3
(1H, dd, J1 � J2 � 7.5 Hz, Ar-H), 7.80 (1H, d, J � 8.0 Hz, Ar-
H), 7.75 (1H, s, -CH � ), 7.62–7.58 (3H, m, Ar-H), 7.53–7.49
(5H, m, Ar-H), 6.85 (2H, d, 3J � 9.0 Hz, Ar-H), and 4.17 (2H, m,
-CH2-); 13C-NMR (δ, ppm): 190.1 (C�S), 166.1, 163.7, 161.2
(C�O), 156.5, 152.7, 147.7, 136.5, 136.2 135.3, 134.0, 130.5,
130.1, 129.9, 127.0, 126.9, 126.6, 120.1, 120.0, 112.8 and 110.9
(CAr), 34.6 (-CH2-), and 39.4 (-N(CH3)2); HR-ESI-MS m/z
574.1050 (M + H)+ calcd. for (C28H24N5O3S3) 574.1041 (see
S5a–S5d from Supporting Information).
3.5.4. N-(5-(4-Fluorobenzylidene)-4-oxo-2-thioxothiazolidin-
3-yl)-2-((4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)
acetamide (6d). Yield: 62.0%; mp: 262–263°C; IR (], cm− 1):
3204 (N-H), 2990 (Csp3-H), 1736, 1686 (C�O), 1593, 1553,
1
1508 (C�N, C�C), and 1240 (-N-C�S); H-NMR (δ, ppm):
3.5.2. N-(5-(4-Bromobenzylidene)-4-oxo-2-thioxothiazolidin-3-yl)-
2-((4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)acetamide
(6b). Yield: 56.0%; mp: 224–225°C; IR (], cm− 1): 3192 (N-
H), 3009 (Csp2-H), 2918 (Csp3-H), 1736, 1688 (C�O), 1601,
11.48 (1H, s, NH), 8.10 (1H, d, 3J � 8.0 Hz, Ar-H), 7.94 (1H, s,
–CH � ), 7.89 (1H, dd, 3J1 � J2 � 8.0 Hz, Ar-H), 7.80–7.76 (3H,
3
m, Ar-H), 7.63–7.61 (3H, m, Ar-H), 7.53–7.49 (3H, m, Ar-H),
7.43 (2H, dd, 3J1 � J2 � 9.0 Hz, Ar-H), and 4.18 (2H, m, -CH2-);
3
1
1578, 1551 (C�N, C�C), and 1254 (-N-C�S); H-NMR (δ,
13C-NMR (δ, ppm): 190.4 (C�S), 166.2, 163.5, 161.2 (C�O),
163.9 (1JC-F � 251.0), 156.5, 147.6, 136.2, 135.3, 134.1, 134.0,
133.9, 130.6, 130.1, 129.9, 127.0, 126.9, 126.6, 120.0, 119.5, and
117.3 (2JC-F � 22.0) (CAr), 34.5 (-CH2-); HR-ESI-MS m/z
549.0527 (M + H)+ calcd. for (C26H18FN4O3S3) 549.0520 (see
S8a–S8c from Supporting Information).
ppm): 11,47 (1H, s, NH), 8.01 (1H, d, 3J � 7.5 Hz, Ar-H), 7.98
3
(1H, s, –CH � ), 7.78 (1H, d, J � 7.5 Hz, Ar-H), 7.71–7.67
(3H, m, Ar-H), 7.54–7.51 (5H, m, Ar-H), 7.43–7.39 (4H, m,
Ar-H), and 4.17 (2H, m, -CH2-); 13C-NMR (δ, ppm): 190.3
(C�S), 166.2, 163.5, 161.2 (C�O), 156.5, 147.6, 136.5, 136.2,
135.3, 133.8, 133.0, 132.1, 130.6, 130.1, 130.07, 129.9, 127.0,
126.6, 120.5, and 120.0 (CAr), 34.5 (-CH2-); HR-ESI-MS m/z
608.9667 (M + H)+ calcd. for (C26H18BrN4O3S3) 608.9724
(see S6a–S6d from Supporting Information).
3.5.5. N-(5-(2-Fluorobenzylidene)-4-oxo-2-thioxothiazolidin-
3-yl)-2-((4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)
acetamide (6e). Yield: 61.0%; mp: 264–265°C; IR (], cm− 1):
3256 (N-H), 2978 (Csp3-H), 1738, 1690 (C�O), 1605, 1551,
1487 (C�N, C�C), and 1258 (-N-C�S); 1H-NMR (δ, ppm):
11.59 (1H, s, NH), 8.10 (1H, d, 3J � 7.5 Hz, Ar-H), 7.89 (1H,
3.5.3. N-(5-(4-Chlorobenzylidene)-4-oxo-2-thioxothiazolidin-3-yl)-
2-((4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)acetamide (6c).
Yield: 60.0%; mp: 226–228°C; IR (], cm− 1): 3190 (N-H), 3009
(Csp2-H), 2920 (Csp3-H), 1738, 1688 (C�O), 1600, 1580, 1551
dd, 3J1 � J2 � 8.0 Hz, Ar-H), 7.86 (1H, s, –CH � ), 7.79 (1H, d,
3
3J � 8.5 Hz, Ar-H), 7.66–7.61 (5H, m, Ar-H), 7.53–7.41 (5H,
1
(C�N, C�C), and 1254 (-N-C�S); H-NMR (δ, ppm): 11.55
m, Ar-H), and 4.18 (2H, m, -CH2-); 13C-NMR (δ, ppm):

4
Journal of Chemistry
190.3 (C�S), 166.3, 163.4, 161.2 (C�O), 161.1 (1JC-F � 251.6),
156.5, 147.6, 136.2, 135.3, 134.2, 130.6, 130.5, 130.1, 129.9,
127.0, 126.6, 126.4 (2JC-F � 21.6), 126.3, 126.2, 122.5, 121.1,
121.0, 120.0 (CAr), and 116.9 (2JC-F � 21.1), 34.5 (-CH2-); HR-
ESI-MS m/z 549.0462 (M + H)+ calcd. for (C26H18FN4O3S3)
549.0520 (see S9a–S9c from Supporting Information).
(M + H)+ calcd. for (C26H19N4O4S3) 547.0563 (see S12a–
S12c from Supporting Information).
3.5.9. N-(5-Benzylidene-4-oxo-2-thioxothiazolidin-3-yl)-2-
((4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl−)t1hio)acetamide
(6i). Yield: 56.0%; mp: 272–273°C; IR (], cm ): 3253 (N-H),
2918 (Csp3-H), 1728, 1694 (C�O), 1605, 1577, 1553 (C�N,
C�C), and 1261 (-N-C�S); 1H-NMR (δ, ppm): 11.54 (1H, s,
3.5.6. N-(5-(4-Methoxybenzylidene)-4-oxo-2-thioxothiazolidin-
3-yl)-2-((4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)acet-
amide (6f). Yield: 54.0%; mp: 218–219°C; IR (], cm− 1) 3208
(N-H), 3009 (Csp2-H), 2920 (Csp3-H), 1736, 1686 (C�O),
1578, 1551, 1506 (C�N, C�C), and 1248 (-N-C�S); 1H-NMR
3
NH), 8.10 (1H, d, J � 7.5 Hz, Ar-H), 7.92 (1H, s, –CH � ),
3
7.89 (1H, dd, 3J1 � J2 � 8.0 Hz, Ar-H), 7.79 (1H, d, 3J � 8.0 Hz,
Ar-H), 7.69 (2H, d, J � 7.5 Hz, Ar-H), 7.64–7.48 (9H, m,
Ar-H), and 4.17 (2H, m, -CH2-); 13C-NMR (δ, ppm): 190.5
(C�S), 166.2, 163.5, 161.2, 156.5, 147.6, 136.2, 135.3, 135.2,
133.2, 131.8, 131.3, 130.6, 130.1, 130.0, 129.9, 127.0, 126.6,
120.0, and 119.8 (CAr), 34.53 (-CH2-); HR-ESI-MS m/z
554.0449 (M + Na)+ calcd. for (C26H18N4O3S3Na) 553.0433
(see S13a–S13c from Supporting Information).
3
(δ, ppm) 11.51 (1H, s, NH), 8.10 (1H, d, J � 8.0 Hz, Ar-H),
7.93 (1H, s, –CH � ), 7.89 (1H, dd, J1 � J23� 8.0, Ar-H), 7.79
3
(1H, d, J � 8.0 Hz, Ar-H), 7.72 (2H, d, J � 9.0 Hz, Ar-H),
3
7.64 (2H, d, J � 8.5 Hz, Ar-H), 7.63–7.61 (3H, m, Ar-H),
7.53–7.48 (3H, m, Ar-H), 4.18 (2H, m, -CH2-), and 3.86 (3H,
s, –OCH3); 13C-NMR (δ, ppm) 190.4 (C�S), 166.2, 163.6,
162.3, 161.2, 156.5, 147.7, 136.2, 135.3, 135.27, 133.7, 130.5,
129.9, 127.0, 126.9, 126.6, 125.8, 120.0, 116.3 and 115.7(CAr),
56.13 (-OCH3), and 34.55 (-CH2-); HR-ESI-MS m/z
561.0731 (M + H)+ calcd. for (C27H21N4O4S3) 561.0647 (see
S10a–S10c from Supporting Information).
3.5.10. N-(5-(4-Nitrobenzylidene)-4-oxo-2-thioxothiazolidin-
3-yl)-2-((4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)acet-
amide (6j). Yield: 53.0%; mp: 233–234°C; IR (], cm− 1): 3265
(N-H), 3067 (Csp2-H), 2972, 2918 (Csp3-H), 1734, 1682
(C�O), 1602, 1551, 1524, 1468 (C�N, C�C), and 1260 (-N-
1
C�S); H-NMR (δ, ppm): 11.61 (1H, s, NH), 8.37 (2H, d,
J � 8.5 Hz, Ar-H), 8.10 (1H, d, 3J � 7.5 Hz, Ar-H), 8.04 (1H, s,
–CH � ), 7.95 (2H, d, J � 8.5, Ar-H), 7.89 (1H, dd, J1 � J2 � 8.0,
Ar-H), 7.79 (1H, d, J � 8.0 Hz, Ar-H), 7.63–7.61 (3H, m, Ar-
H), 7.53–7.49 (3H, m, Ar-H), and 4.19 ppm (2H, m, -CH2-);
13C-NMR (δ, ppm): 187.8 (C�S), 167.3, 162.9, 161.0, 158.8,
148.3, 146.7, 138.8, 135.3, 135.0, 131.2, 131.0, 130.7, 130.1,
129.1, 127.8, 127.0, 125.3, 124.7, 124.5, and 119.9 (CAr), 34.5
(-CH2-); HR-ESI-MS m/z 576.0445 (M + H)+ calcd. for
(C26H18N5O5S3) 576.0464 (see S14a–S14a from Supporting
Information).
3.5.7. N-(5-(4-Hydroxybenzylidene)-4-oxo-2-thioxothiazolidin-
3-yl)-2-((4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)acet-
amide (6g). Yield: 57.0%; mp: 215–216°C; IR (], cm− 1): 3196
(br) (O-H, N-H), 3013 (Csp2-H), 2918 (Csp3-H), 1728, 1711,
1651 (C�O), 1572, 1551, 1468 (C�N, C�C), and 1246
(-N-C�S); 1H-NMR (δ, ppm): 11.48 (1H, s, NH), 10.57 (1H,
s, OH), 8.10 (1H, d, 3J � 7.5 Hz, Ar-H), 7.89 (1H, dd,
3
3J1 � J2 � 8.0 Hz, Ar-H), 7.82 (1H, s, –CH � ), 7.79 (1H, d,
3J � 8.0 Hz, Ar-H), 7.63–7.60 (3H, m, Ar-H), 7.56 (2H, d,
3J � 8.5 Hz, Ar-H), 7.52–7.48 (3H, m, Ar-H), 6.96 (2H, d,
3J � 8.5 Hz, Ar-H), and 4.17 (2H, m, -CH2-); 13C-NMR (δ,
ppm): 190.5 (C�S), 166.2, 163.7, 162.8, 161.5, 161.2, 156.5,
147.6, 136.2, 135.8, 135.3, 134.2, 130.5, 130.1, 129.9, 127.0,
126.9, 126.6, 124.3, 120.0, 117.2, and 115.0 (CAr), 34.5 (-CH2-);
HR-ESI-MS m/z 547.0598 (M + H)+ calcd. for
(C26H19N4O4S3) 547.0568 (see S11a–S11c from Supporting
Information).
3.5.11. N-(5-(3-Nitrobenzylidene)-4-oxo-2-thioxothiazolidin-
3-yl)-2-((4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)
acetamide (6k). Yield: 51.0%; mp: 200–201°C; IR (], cm− 1):
3557, 3418, 3179 (N-H), 3011 (Csp2-H), 2924 (Csp3-H), 1736,
1682 (C�O), 1543, 1466 (C�N, C�C), and 1250 (-N-C�S);
1H-NMR (δ, ppm): 11.60 (1H, s, NH), 8.55 (1H, s, Ar-H),
8.35 (1H, dd, 3J � 8.0, 4J � 2.0 Hz, Ar-H), 8.10 (1H, s, –CH � ),
8.09 (2H, m, Ar-H), 7.91–7.84 (2H, m, Ar-H), 7.80 (1H, d,
3J � 8.0 Hz, Ar-H), 7.63–7.61 (3H, m, Ar-H), 7.53–7.49 (3H,
m, Ar-H), and 4.19 (2H, m, -CH2-); 13C-NMR (δ, ppm):
190.3 (C�S), 166.3, 163.3, 161.2, 156.5, 148.8, 147.6, 136.4,
136.2, 135.3, 134.8, 132.7, 131.6, 130.6, 130.1, 129.9, 127.0,
126.6, 125.9, 125.7, 122.8, and 120.0, (CAr), 34.51 (-CH2-);
HR-ESI-MS m/z 576.0468 (M + H)+ calcd. for (C26H18N5O5S3)
576.0470 (see S15a–S15c from Supporting Information).
3.5.8. N-(5-(3-Hydroxybenzylidene)-4-oxo-2-thioxothiazolidin-
3-yl)-2-((4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)acet-
amide (6h). Yield: 54.0%; mp: 233–234°C; IR (], cm− 1): 3447
(br, O-H, N-H), 1734, 1654 (C�O), 1607, 1576, 1554, and
1253 (-N-C�S); 1H-NMR (δ, ppm): 11.53 (1H, s, NH), 10.48
3
(1H, s, OH), 8.10 (1H, d, J � 7.0 Hz, Ar-H), 7.89 (1H, dd,
3
3J1 � J2 � 8.0 Hz, Ar-H), 7.82 (1H, s, –CH � ), 7.79 (1H, d,
3J � 8.0 Hz, Ar-H), 7.63–7.61 (3H, m, Ar-H), 7.53–7.48 (3H,
3
m, Ar-H), 7.38 (1H, dd, 3J1 � J2 � 8.0 Hz, Ar-H), 7.13 (1H, d,
3J � 7.5 Hz, Ar-H), 7.05 (1H, s, Ar-H), 6.95 (1H, dd,
3J � 8.0 Hz, 4J � 2.0 Hz, Ar-H), and 4.18 (2H, m, -CH2-); 13C-
NMR (δ, ppm): 190.08 (C�S), 165.7, 163.0, 160.6 (C�O),
158.0, 156.0, 147.1, 135.6, 134.9, 134.7, 133.8, 130.6, 130.0,
129.5, 129.4, 126.5, 126.4, 126.1, 122.2, 119.5, 119.0, 118.7,
and 116.5 (CAr), 34.0 (-CH2-); HR-ESI-MS m/z 547.0570
3.5.12. N-(5-(2-Nitrobenzylidene)-4-oxo-2-thioxothiazolidin-
3-yl)-2-((4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)
acetamide (6l). Yield: 63.0%; mp: 230–231°C; IR (], cm− 1):
3252 (N-H), 2974 (Csp3-H), 1740, 1686 (C�O), 1603, 1551,
1
1524, 1468 (C�N, C�C), and 1250 (-N-C�S); H-NMR (δ,
ppm) 11.59 (1H, s, NH), 8.26 (1H, d, 3J � 8.0, Ar-H), 8.17 (1H,

Journal of Chemistry
5
s, –CH � ), 8.10 (1H, d, 3J � 8.0, Ar-H), 7.96–7.87 (2H, m, Ar-
H), 7.80–7.77 (3H, m, Ar-H), 7.64–7.58 (3H, m, Ar-H),
7.52–7.49 (3H, m, Ar-H), and 4.18 (2H, m, -CH2-); 13C-
NMR (δ, ppm) 190.7 (C�S), 166.3, 162.8, 161.2 (C�O),
156.5, 148.3, 147.6, 136.2, 135.3, 132.4, 132.2, 130.6, 130.1,
130.0, 129.9, 128.9, 127.0, 126.95, 126.6, 126.2, 124.1, and
120.0 (CAr), 34.5 (-CH2-); HR-ESI-MS m/z 576.0427
(M + H)+ calcd. for (C26H18N5O5S3) 576.0470 (see S16a–
S16c from Supporting Information).
163.0, 161.2 (C�O), 156.5, 147.6, 146.9, 136.2, 135.9, 135.7,
135.3, 130.8, 130.5, 130.1, 129.9, 129.5, 128.8, 127.0,
126.9, 126.6, 123.5, 120.7, and 120.0 (CAr and Cankene), 34.5
(-CH2-); HR-ESI-MS m/z 557.0791 (M + H)+ calcd. for
(C28H21N4O3S3) 557.0770 (see S19a–S19c from Supporting
Information).
3.6. Cell Viability Assay. )e experimental procedure was
followed by the steps presented in the literature [46, 47]. In
brief, K562 cells and MCF7 cells were cultured in the DMEM
medium supplemented with 10% fetal bovine serum (FBS),
100 IU/mL penicillin, and 100 μg/mL streptomycin and
maintained at 37°C and 5% CO2 with 95% humidity. Viable
cells were counted and inoculated in 96-well plate with a
density of 105 cells/100 μL/well for K562 and 5 ×104 cells/
100 μL/well for MCF7. After 24 hours, the cells were treated
with the compounds and doxorubicin (positive control)
diluted in culture media at 100, 50, 25, 12.5, 6.25, 3.125, and
0 μg/mL concentration containing 1, 0.5, 0.25, 0.125, 0.0625,
0.03125, and 0% dimethyl sulfoxide (DMSO), respectively.
DMSO in culture media was used as negative control. In
addition, the culture medium without cells was used as
blank. All experiments were done in triplicate. )e plates
were incubated in 5% CO2 and 95% humidity at 37°C for
72 hours. 10 μL of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphe-
nyltetrazolium bromide (MTT) was added into each well
and incubated in 37°C in 5% CO2 for 3.5 hours. 70 μL of
detergent reagent (10% SDS) was added into each well, and
the plate was maintained in 37°C for 16 hours. )e optical
density of each well was read by using a scanning multiwall
spectrophotometer (Sunrise) at a wavelength of 595 nm. Cell
survival was measured as the percentage absorbance com-
pared to the negative control (DMSO-treated cells). Cell
death (% inhibition) was estimated by the following formula:
3.5.13. N-(5-(Benzo[d][1,3]dioxol-5-yl-methylene)-4-oxo-2-thi-
oxothiazolidin-3-yl)-2-((4-oxo-3-phenyl-3,4-dihydroquinazolin-
2-yl)thio)acetamide (6m). Yield: 62.0%; mp: 231–232°C; IR
(], cm− 1) 3429, 3103, 3051 (Csp2-H), 2974 (Csp3-H), 2778,
2457, 1776, 1713, 1632 (C�O), 1607, 1573, 1492 (C�N,
C�C), and 1244 (-N-C�S); 1H-NMR (δ, ppm) 11.51 (1H, s,
3
NH), 8.10 (1H, d, 3J � 7.5, Ar-H), 7.88 (1H, dd, 3J1 � J2 � 7.5,
3
Ar-H), 7.84 (1H, s, –CH � ), 7.79 (1H, d, J � 8.0, Ar-H),
7.64–7.61 (3H, m, Ar-H), 7.53–7.49 (3H, m, Ar-H), 7.27 (1H,
d, 3J � 8.0, Ar-H), 7.22 (1H, s, Ar-H), 7.14 (1H, d,3J � 8.5, Ar-
H), 6.17 (2H, s,-OCH2-), and 4.18 (2H, m, -CH2-); 13C-NMR
(δ, ppm) 190.3 (C�S), 166.2, 163.6, 161.2 (C�O), 156.5,
150.7, 148.9, 147.6, 136.2, 135.4, 135.3, 130.5, 130.1, 129.9,
127.9, 127.4, 127.0, 126.9, 126.6, 120.0, 117.0, 110.3 and 109.9
(CAr), 102.8 (-OCH2O-), and 34.5 (-CH2-); HR-ESI-MS m/z
597.0361 (M + Na)+ calcd. for (C27H18N4O5S3Na) 597.0337
(see S17a–S17c from Supporting Information).
3.5.14. N-(5-(4-Hydroxy-3-methoxybenzylidene)-4-oxo-2-thio-
xothiazolidin-3-yl)-2-((4-oxo-3-phenyl-3,4-dihydroquinazolin-
2-yl)thio)acetamide (6n). Yield: 58.0%; mp: 234–235°C; IR
(], cm− 1) 3358, 3290, 3063 (Csp2-H), 2978, 2932 (Csp3-H),
2851, 1728, 1682 (C�O), 1572, 1549, 1497 (C�N, C�C), and
1249 (-N-C�S); 1H-NMR (δ, ppm) 11.48 (1H, s, NH), 10.24
(1H, s, OH), 8.10 (1H, d, 3J � 7.5, Ar-H), 7.89 (1H, dd,
A
Sample − ABlank
ꢀ
ꢁ
(1)
% inhibition � 100 −
100,
3
3J1 � J2 � 7.5, Ar-H), 7.83 (1H, s, –CH � ), 7.80 (1H, d, J � 8.0,
A
DMSO − ABlank
ꢂ
ꢃ
Ar-H), 7.63–7.61 (3H, m, Ar-H), 7.53–7.49 (3H, m, Ar-H),
4
3
where ASample is the absorbance of sample at 595 nm, ADMSO
is the absorbance of negative control at 595 nm, and ABlank is
the absorbance of blank at 595 nm.
Statistical analyses were performed using GraphPad
Prism version 5.0 software.
7.25 (1H, d, J � 1,5 Hz, Ar-H), 7.18 (1H, dd, J � 8.5 Hz,
4J � 2.0 Hz, Ar-H), 6.97 (1H, d, 3J � 8.0 Hz, Ar-H), 4.17 (2H,
m, -CH2-), and 3.85 (3H, s, –OCH3); 13C-NMR (δ, ppm)
190.4 (C�S), 166.2, 163.7, 161.2 (C�O), 156.5, 151.1, 148.7,
147.7, 136.2, 136.1, 135.3, 130.6, 130.1, 129.9, 127.0, 126.9,
126.6, 126.1, 124.7, 120.0, 117.0, 115.4, and 115.1 (CAr), 56.2
(-OCH3), 34.5 (-CH2-); HR-ESI-MS m/z 577.0659 (M + H)+
calcd. for (C27H21N4O5S3) 577.0668 (see S18a–S18c from
Supporting Information).
4. Results and Discussion
2-Mercapto-3-phenylquinazolin-4-one (2), ethyl 2-((4-oxo-
3-phenyl-3,4-dihydroquinazolin-2-yl)thio)acetate (3), and
2-((4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)aceto-
hydrazide (4) were prepared according to reported methods
[1, 3, 7, 14, 15, 18]. )e similarity in both melting points and
spectral characteristics of these compounds with the ones of
the corresponding compounds in literature confirmed their
formation.
3.5.15. 2-((4-Oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)-
N-(4-oxo-5-(phenylallylidene)-2-thioxothiazolidin-3-yl)acet-
amide (6o). Yield: 60.0%; mp: 246–247°C; IR (], cm− 1) 3233
(N-H), 2920 (Csp3-H), 2851, 1740, 1690 (C�O), 1607, 1578,
1
1551, 1470 (C�N, C�C), and 1246 (-N-C�S); H-NMR (δ,
ppm) 11.48 (1H, s, NH), 8.10 (1H, d, 3J � 8.0, Ar-H), 7.89 (1H,
)e reaction of a hydrazide compound with thio-
3
3
3
dd, J1 � J2 � 8.5, Ar-H), 7.79 (1H, d, J � 8.0, Ar-H), 7.73
(2H, d, 3J � 7.0, Ar-H), 7.65 (1H, d, 3J � 12.0 Hz, –CH�CH-),
7.61–7.58 (3H, m, Ar-H), 7.53–7.49 (4H, m, Ar-H), 7.46–
carbonyl-bis-thioglycolic acid to form
a
2-thio-
xothiazolidine-4-one compound was mentioned by some
authors [36,38–43]. )erefore, the hydrazide 4 was used in
the reaction with thiocarbonyl-bis-thioglycolic acid in
ethanol to obtain N-(4-oxo-2-thioxothiazolidin-3-yl)-2-
7.31 (3H, m, Ar-H), 7.16 (1H, dd, 3J1 � J2 �12.0, Ar-H), and
3
4.16 (2H, m, -CH2-); 13C-NMR (δ, ppm) 190.4 (C�S), 166.2,

6
Journal of Chemistry
Table 1: )e selective cytotoxicity of compounds 5 and 6a–o
((4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)acetamide
(5). In the IR spectrum of compound 5, beside the absorption
peak of the –NH– group at 3202 cm− 1 and the absorption peak
of lactam and amide carbonyl groups at 1690 cm− 1, the ap-
pearance of a new band at 1759 cm–1 indicated the presence of
the C�O group in the 2-thioxothiazolidin-4-one ring. )e mass
spectrum of the product showed the [M + H]+ ion peak at m/z
443.0367 in agreement with the molecular formula of
against K562 and MCF7 cell lines
Inhibition of cell growth (%)
No
Compounds
K562
MCF7
1
Doxorubicin
99.1 0.3
7.6 0.6
23.4 0.6
13.5 0.7
4.6 0.1
34.4 2.7
36.6 2.0
22.9 0.6
8.4 1.1
33.0 0.7
15.7 2.3
52.7 1.0
38.0 2.1
22.2 1.3
18.1 1.2
23.4 2.0
3.0 0.1
96.5 1.3
64.4 6.5
51.3 0.4
14.8 3.3
38.2 1.3
22.2 0.9
33.6 2.3
82.5 5.2
23.8 0.4
7.7 0.1
27.1 0.6
11.7 0.5
37.1 2.8
64.4 2.1
9.8 0.4
2
5
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
6l
6m
6n
6o
3
4
1
C19H15N4O3S3 ((M + H) � 443.0306). In the H-NMR spec-
5
trum of the compound, besides the signal of the methylene
group bonding with the quinazoline ring via the sulfur atom at
δ 4.13, there was an appearance of a new signal at δ 4.41, which
was imputed to the methylene group on the thiazolidinone ring.
Similar to the 3-(4-methylcoumarin-7-yloxyacetylamino)-2-
thioxo-1,3-thiozolidin-4-one compound [36], the signals of the
methylene groups in the molecule of compound 5 were not also
singlets as expected. )ey were split by a non-first-order
splitting effect.17 signals appeared in the 13C-NMR spectrum of
5 including 2 signals at δ 34.5 and 33.8 (2 methylene carbon), a
signal at δ 200.1 (carbon in the thioxo group), 3 signals at δ
170.5, 166.0, and 161.2 (3 carbon carbonyl), and 14 signals at δ
120.0–156.5 (unsaturated and aromatic carbon) are good ac-
cordant to the structure of compound 5.
6
7
8
9
10
11
12
13
14
15
16
17
21.0 1.0
15.5 0.4
Table 2: IC50 (μg/mL) on two cancer cell lines of the compounds.
IC50 (μg/mL)
Compound 5 with the 2-thioxothiazolidin-4-one ring
containing the active methylene group was then further
reacted with appropriate aldehydes to give the raw of N-(5-
arylidene-4-oxo-2-thioxothiazolidin-3-yl)-2-((4-oxo-3-phe-
nyl-3,4-dihydroquinazolin-2-yl)sulfanyl)acetamide com-
pounds (6a–o) in the conditions of the Knoevenagel
condensation reaction. In the IR spectra, the signal of the
C�O group in the thioxothiazolidin-4-one ring of the 6a–o
compounds in a comparison with that one of the compound 5
appeared at a lower frequency because of the conjugation of
the carbonyl group with the benzylidene moiety. Mass spectra
of the synthesized 6a–o compounds showed the molecular
peaks in agreement with their molecular formula. In the 1H-
NMR spectra of 6a–o compounds, the signals of the meth-
ylene group outside the thiazolidinone ring (-SCH2CONH-)
still appeared as multiplet peaks at around δ 4.16–4.19, but the
signal of the methylene group on the ring was disappearance.
Along with the additional signals of the aromatic protons in
accordance with those ones of the initial aldehyde, a signal of
the methylidene proton as a singlet at δ 7.79–7.93 also
appeared in the spectrum of each compound. )ese were
evidence for the conversion of compound 5 to compounds
6a–h by Knoevenagel condensation. According to the pre-
vious reports [21, 22, 24, 25, 43, 48], because of the interaction
with the carbonyl group at the 4 position, the methylidene
proton of the Z-isomer of 5-arylidene-2-thioxo-thiazolidin-4-
one compounds was more downfield (δ 7.9) than that of the
No
Compounds
K562
MCF7
1
2
3
4
5
6
7
8
Doxorubicin
1.8 0.1
>100
>100
>100
>100
>100
>100
>100
2.4 0.1
58.1 3.8
98.0 0.4
>100
5
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
6l
6m
6n
6o
>100
>100
>100
65.4 7.6
9
>100
>100
>100
10
11
12
13
14
15
16
17
>100
>100
>100
93.8 0.7
>100
>100
>100
>100
87.4 2.2
>100
>100
>100
>100
>100
>100
)e experiments were done in triplicate. )e presented data show
mean SD. )e values were calculated by using GraphPad Prism 5 software.
in terms of the percentage growth inhibition (Table 1) and
the IC50 value of the compounds (Table 2). )e results
showed that compounds 5, 6f, and 6l exert moderate cyto-
toxicity against MCF7 cells with a % inhibition of cell growth
of 64.4 6.5 μg/mL, 82.5 5.2 μg/mL, and 64.4 2.1 μg/mL,
respectively. Other compounds showed mild proliferative
inhibition on both tested tumor cell lines.
1
E-isomer (δ 7.4). Comparing the vinylic proton shift in H-
NMR spectra of 6a–o with these chemical shifts indicated that
the exocyclic double bond of the thiazolidinone 6a–o com-
pounds exists in the Z-configuration. )e formation of the Z-
isomers may be explained by the high degree of thermody-
namic stability of these isomers [21, 22, 24].
5. Conclusions
In the present paper, a new compound named N-(4-oxo-
2-thioxothiazolidin-3-yl)-2-((4-oxo-3-phenyl-3,4-dihy-
droquinazolin-2-yl)thio)acetamide (5) and fourteen new
5-arylidene derivatives of this compound were successfully
All compounds were evaluated for their potential cy-
totoxicity against K562 and MCF7 tumor cell lines using
doxorubicin as a positive control. )e results were expressed

Journal of Chemistry
7
promising anticonvulsant activity,” Acta Pharmaceutica,
vol. 53, pp. 127–138, 2003.
[8] A. S. El-Azab, S. G. Abdel-Hamide, M. M. Sayed-Ahmed et al.,
“Novel 4(3H)-quinazolinone analogs: synthesis and anti-
convulsant activity,” Medicinal Chemistry Research, vol. 22,
no. 6, pp. 2815–2827, 2013.
[9] V. Alagarsamy, R. Giridhar, and M. R. Yadav, “Synthesis and
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synthesized and then the structure was determined by IR,
1H-NMR, 13C-NMR, and HR-MS spectral data. )e investigation
also indicated that the Z-isomer of the N-(5-arylidene-4-oxo-2-
thioxothiazolidin-3-yl)-2-((4-oxo-3-phenyl-3,4-dihydroquinazolin-
2-yl)thio)acetamide compounds was formed in the Knoe-
venagel reaction of (5) and appropriate aldehydes. All of the 5
arylidene derivatives exhibited mild-to-moderate cytotoxic
activity against K562 and MCF7 cell lines.
Data Availability
)e IR, NMR, and HR-MS spectral data used to support the
findings of this study are included within the supplementary
information file.
Conflicts of Interest
)e authors declare that there are no conflicts of interest
regarding the publication of this paper.
[12] A. Gu¨rsoy and N. Karal, “Synthesis and primary cytotoxicity
evaluation of 3-[[(3-phenyl-4(3H)-quinazolinone-2-yl)
mercaptoacetyl]hydrazono]-1H-2-indolinones,” European
Journal of Medicinal Chemistry, vol. 38, no. 6, pp. 633–643,
2003.
Acknowledgments
)is work was supported by the Ministry of Education and
Training of Vietnam (Grant no. B2019-SPS-02).
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Sayed, “Synthesis and antitumor activity of some 2,3-di-
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Medicinal Chemistry, vol. 45, no. 12, pp. 6058–6067, 2010.
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Supplementary Materials
Supplementary data associated with this article can be found
in the attached file. )ese data include IR, H-NMR, 13C-
1
NMR, and HR-MS spectra of the synthesized compounds (2,
3, 4, 5, and 6a–o). (Supplementary Materials)
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