Synthesis and in vitro antiproliferative activity of 2,5-disubstituted-1,3, 4-oxadiazoles containing trifluoromethyl benzenesulfonamide moiety

Article abstract of DOI:10.1007/s00044-014-0918-z

A series of new 2,5-disubstituted-1,3,4-oxadiazoles 6(a-j) have been conveniently synthesized by intermolecular oxidative cyclization of (E)-2-(arylbenzylidene)-2-[(4-methoxyphenyl)amino]acetohydrazides promoted by iodobenzene diacetate as an oxidant. The synthesized compounds were characterized by elemental analyses, FT-IR, LCMS, ¹H NMR, and ¹³C NMR spectral studies. All the compounds were evaluated for their in vitro antiproliferative effect using the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyl tetrazolium bromide assay method against four human cancer cell lines (K562, Colo-205, MDA-MB 231, IMR-32) for the time period of 24 h. Among the analogs, compounds 6h and 6i showed good activity on all cell lines, whereas the other compounds in the series exhibited moderate activity.

Full text of DOI:10.1007/s00044-014-0918-z

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res
DOI 10.1007/s00044-014-0918-z
ORIGINAL RESEARCH
Synthesis and in vitro antiproliferative activity
of 2,5-disubstituted-1,3,4-oxadiazoles containing
trifluoromethyl benzenesulfonamide moiety
•
Basavapatna N. Prasanna Kumar Kikkeri N. Mohana
•
•
Lingappa Mallesha Bantal Veeresh
Received: 2 September 2013 / Accepted: 15 January 2014
Ó Springer Science+Business Media New York 2014
Abstract A series of new 2,5-disubstituted-1,3,4-oxadi-
azoles 6(a–j) have been conveniently synthesized by
intermolecular oxidative cyclization of (E)-2-(arylbenzy-
lidene)-2-[(4-methoxyphenyl)amino]acetohydrazides pro-
moted by iodobenzene diacetate as an oxidant. The
synthesized compounds were characterized by elemental
Introduction
Cancer treatment has been a major endeavor of research
and development in academia and pharmaceutical industry
for the last many years as it is one of the leading causes of
death (Jermal et al., 2008). A variety of anticancer drugs
are currently in clinical use and some of these drugs can be
applied successfully for the treatment of several neoplastic
diseases such as leukemia or testicular cancer. Still cancer
remains the leading cause of death in developing and
developed countries. Many of the available anticancer
agents exhibit undesirable side effects such as reduced
bioavailability, toxicity, and drug-resistance (Eckhatdt,
2002; Altmann, 2001; O’Dwyer and Druker, 2001).
Therefore, the search for novel and selective anticancer
agents is urgently required due to problems associated with
currently available anticancer drugs.
1
analyses, FT-IR, LCMS, H NMR, and 13C NMR spectral
studies. All the compounds were evaluated for their in vitro
antiproliferative effect using the 3-(4,5-dimethylthiazol-2-
yl)-2,5-diphenyl tetrazolium bromide assay method against
four human cancer cell lines (K562, Colo-205, MDA-MB
231, IMR-32) for the time period of 24 h. Among the
analogs, compounds 6h and 6i showed good activity on all
cell lines, whereas the other compounds in the series
exhibited moderate activity.
Keywords 2,5-Disubstituted-1,3,4-oxadiazoles ꢀ
MTT assay ꢀ Antiproliferative activity ꢀ
Human cancer cell lines
1,3,4-Oxadiazoles are important class of heterocyclic
compounds with a broad range of biological activities such
as analgesic (Gilani et al., 2010), antimicrobial (Sahin
et al., 2002), antiviral (Wang et al., 2012), anticonvulsant
(Bondock et al., 2012), antihypertensive (Bankar et al.,
2009), antiproliferative (Liu et al., 2012), enzyme Inhibi-
tors (Gosselin et al., 2010), and 5-HT-receptor antagonists
(Liao et al., 2000). The five-member 1,3,4-oxadiazole
heterocycles are also useful intermediates in organic syn-
thesis (Warrener, 2000). 2,5-Disubstituted-1,3,4-oxadiaz-
ole derivatives possess broad spectrum of pharmacological
activities such as anticancer (Rahman, 2013), antimicro-
bial, and antiviral (Somani et al., 2011).
B. N. Prasanna Kumar ꢀ K. N. Mohana (&)
Department of Studies in Chemistry, University of Mysore,
Manasagangotri, Mysore 570 006, India
e-mail: drknmohana@gmail.com
L. Mallesha
PG Department of Chemistry, JSS College of Arts, Commerce
and Science, Ooty Road, Mysore 570 025, India
The chemistry of fluorine-containing compounds has
been tremendously developed owing to their unique prop-
erties such as high-thermal stability and lipophilicity. Their
biological studies clearly indicate that the presence of tri-
fluoromethyl group gives useful biological activity, and the
B. Veeresh
Department of Pharmacology, G Pullareddy College of
Pharmacy, Mehdipatnam, Hyderabad, India
123

Med Chem Res
subject is of considerable growing interest (Plant, 2004).
The increased activity is attributed to the presence of
fluorine atoms (highly electronegative) in the molecules
which increase the lipophilicity and affects the partitioning
of molecules into membranes and facilitates hydrophobic
interactions of the molecules with specific binding sites on
either receptor or enzymes. Meanwhile, sulfonamide has
attracted the increasing attention in the supramolecular
chemistry and supramolecular medicinal chemistry (Zhou
et al., 2009). The sulfonamides constitute an important
class of drugs, possessing a host of several types of bio-
logical properties including antifungal (Sisik et al., 2009),
antiviral (Gawin et al., 2008), and antitumor (Bouissane
et al., 2006) in recent years. In connection with such
studies, the synthesis and antiproliferative activity of new
2,5-disubstituted-1,3,4-oxadiazoles against human cancer
cell lines has been reported in this article.
C-2, C-6), 126.2 (CH, JCF = 270 Hz, C-3, C-5), 124.6
(JCF = 270 Hz, CF3), 63.2 (CH2, O–CH2CH3), 43.4 (NH–
CH2), 14.5 (CH3); Anal. Calcd. for C11H11N: C, 42.58; H,
3.57; N, 4.51. Found: C, 42.71; H, 3.84; N, 4.87.
N-(2-Hydrazinyl-2-oxoethyl)-4-
(trifluoromethyl)benzenesulfonamide (4)
Compound 4 was prepared by refluxing a mixture of ethyl
((4-trifluoromethyl)phenyl)sulfonylglycinate (3) (0.1 mmol)
and hydrazine hydrate (5 ml) in 20 ml of absolute ethanol for
3 h. The reaction mixture was cooled to room temperature,
and the solid obtained was filtered, washed with ethanol. It
wasobtainedasawhitesolid, yield80 %;mp143–145 °C;1H
NMR (DMSO-d6, 400 MHz): d = 7.79 (2H, dd, J = 2.12,
6.93, H-3, H-5), 7.10 (2H, dd, J = 2.18, 6.92 Hz, H-2, H-6),
4.60 (2H, s, –CH2), 4.51 (2H, s, NH2); 13C NMR (DMSO-d6,
100 MHz): d = 170.2 (C, C=O), 140.6 (C, C-1). 134.0 (C,
JCF = 30 Hz, C-4), 128.4 (C-2, C-6), 125.8 (JCF = 4.8 Hz,
C-3, C-5), 124.4 (JCF = 270 Hz, CF3), 45.4 (NH–CH2);
Anal. Calcd. for C9H10N3: C, 36.36; H, 3.39; N, 14.14. Found:
C, 36.51; H, 3.52; N, 14.32.
Experimental
Chemistry
All solvents and reagents were purchased from Merck
chemicals, India. Melting range was determined using
Veego Melting Point VMP III apparatus. Elemental anal-
yses were recorded on Costech ECS 4010 CHNS-O Ele-
mental Analyzer. The FT-IR spectra were recorded using
KBr disks on FT-IR Jasco 4100 infrared spectrophotome-
General procedure for the synthesis of (E)-N-(2-(2-
benzylidenhydrazinyl)-2-oxoethyl)-4-
(trifluoromethyl)benzenesulfonamides (5a–j)
An equimolar mixture of 4 (0.01 mmol) and substituted
benzaldehydes was refluxed in ethanol in the presence of
few drops of acetic acid for 2 h. The progress of the
reaction was monitored by TLC. After completion of the
reaction, the reaction mass was cooled, and the solid
formed was filtered to give corresponding hydrazones.
1
ter. H and 13C NMR spectra were recorded on Bruker
DRX-500 spectrometer at 400 MHz using DMSO-d6 as
solvent. The mass spectra of the samples were recorded
using the instrument LC-MSD-Trap-XCT.
Ethyl((4-trifluoromethyl)phenyl)sulfonylglycinate (3)
(E)-N-(2-(2-Benzylidenhydrazinyl)-2-oxoethyl)-4-
(trifluoromethyl)benzenesulfonamide (5a)
To a stirred solution of glycine ethylester hydrochloride 1
(0.1 mmol), triethylamine (0.25 mmol) was added in 50 ml
of dichloromethane at room temperature. This mixture was
stirred for 5 min, and then 4-(trifluoromethyl)benzenesul-
fonyl chloride 2 (0.1 mmol) was added at this temperature.
The reaction mixture was stirred for 1 h at room temper-
ature and monitored by TLC. After completion of the
reaction, the reaction mixture was washed with water and
then dried with anhydrous sodium sulfate. The solvent was
evaporated to dryness, and the pure product was crystal-
lized from petroleum ether. It was obtained as a white
White needles (MeOH) (this compound was prepared by
the reaction of compound 4 and benzaldehyde. It was
obtained as a white solid); mp 150–151 °C; IR (KBr) mmax
3300, 3150, 3073, 1681, 1631, 1156, 1061 cm-1; 1H NMR
(DMSO-d6, 400 MHz,): d = 9.35 (1H, s, NH). 8.62 (1H, s,
N=CH), 8.14 (2H, d, J = 8.02 Hz, H-20, H-60), 8.01 (1H, s,
NH), 7.62 (3H, m, H-3, H-5), 7.40 (2H, d, J = 8.53 Hz,
H-30, H-50), 7.03 (2H, d, J = 8.51 Hz, H-2, H-6), 4.58 (2H,
d, –CH2); 13C NMR (DMSO-d6, 400 MHz): d = 170.8 (C,
C=O), 145.6 (C, C-1), 144.8 (CH, C=N), 134.2 (C,
JCF = 34.2 Hz, C-4), 131.0 (C, C-10), 129.5 (CH, C-2,
C-6), 128.2 (CH, C-20, C-60), 124.6 (CH, JCF = 4.2 Hz,
C-3, C-5), 124.5 (JCF = 272 Hz, CF3), 116.2 (CH, C-30,
C-50), 115.7 (CH, C-40), 45.4 (NH–CH2); Anal. Calcd. for
C16H14N3: C, 49.87; H, 3.66; N, 10.90. Found: C, 49.33; H,
3.78; N, 10.70.
1
solid, yield 82 %; mp 121–123 °C; H NMR (DMSO-d6,
400 MHz): d = 7.75 (2H, dd, J = 2.16, 6.88, H-3, H-5),
7.12 (2H, dd, J = 2.04, 6.8 Hz, H-2, H-6), 4.59 (2H, s, –
CH2), 4.41 (2H, m, CH2), 1.16 (3H, t, J = 7.2 Hz, –CH3);
13C NMR (DMSO-d6, 100 MHz): d = 170.0 (C, C=O),
147.6 (C, C-1), 134.0 (C, JCF = 270 Hz, C-4), 127.5 (CH,
123

Med Chem Res
C-30), 126.6 (CH, JCF = 4.0 Hz, C-3, C-5), 124.8
(JCF = 272.0 Hz, CF3), 124.0 (CH, C-60), 45.8 (NH–CH2);
Anal. Calcd. for C16H13N3: C, 45.78; H, 3.12; N, 10.01.
Found: C, 45.47; H, 3.31; N, 10.32.
(E)-N-(2-(2-(4-Methylbenzylidene)hydrazinyl)-2-oxoethyl)-
4-(trifluoromethyl)benzene sulfonamide (5b)
White needles (EtOH) (this compound was prepared by the
reaction of compound 4 and 4-methylbenzaldehyde. It was
obtained as a white solid); mp 161–163 °C. IR (KBr) mmax
3320, 3155, 3071, 1671, 1638, 1159, 1060 cm-1; 1H NMR
(DMSO-d6, 400 MHz): d = 9.28 (1H, s, NH), 8.51 (1H, s,
N=CH), 8.03 (1H, s, NH), 7.85–7.98 (4H, m, H-3, H-5,
H-20, H-60), 7.23–7.56 (4H, m, H-2, H-6, H-30, H-50), 4.59
(2H, s, –CH2), 18 (3H, s, –CH3); 13C NMR (DMSO-d6,
100 MHz): d = 171.0 (C, C=O) ppm, 145.6 (C, C-1),
144.7 (CH, C=N), 134.0 (C, JCF = 33.1 Hz, C-4), 130.1
(C-1), 129.2 (C-2, C-6), 126.6 (C-20, C-60), 124.6
(JCF = 4.8 Hz, C-3, C-5), 124.5 (JCF = 271.0 Hz, CF3),
116.2 (C-30, C-50), 115.6 (C-40), 45.3 (NH–CH2), 20.5
(CH3, Ar-CH3); Anal. Calcd. for C17H16N3: C, 51.12; H,
4.04; N, 10.52. Found: C, 51.32; H, 4.21; N, 10.43.
(E)-N-(2-(2-(4-Chlorobenzylidene)hydrazinyl)-2-
oxoethyl)-4-(trifluoromethyl)benzene sulfonamide (5e)
Yellow needles (EtOH) (this compound was prepared by
the reaction of compound 4 and 4-chlorobenzaldehyde. It
was obtained as a yellow solid); mp 167–169 °C; IR (KBr)
1
mmax 3300, 3143, 3070, 1665, 1621, 1158, 1061 cm-1; H
NMR (DMSO-d6, 400 MHz): d = 9.37 (1H, s, NH), 8.62
(1H, s, N=CH), 8.03 (1H, s, NH), 7.97 (2H, d, J = 8.0 Hz,
H-20, H-60), 7.68 (2H, d, J = 8.08 Hz, H-3, H-5), 7.42 (2H,
d, J = 8.51 Hz, H-30, H-50), 7.05 (2H, d, J = 8.51 Hz,
H-2, H-6), 6.36 (s, NH), 4.58 (2H, s, –CH2); 13C NMR
(DMSO-d6, 100 MHz); d = 171.0 (C, C=O), 148.5 (C,
C-1), 144.1 (CH, C=N), 134.4 (C, JCF = 31.5 Hz, C-4),
134.0 (C, C-40), 132.2 (C, C-10), 131.0 (CH, C-20, C-60),
129.4 (CH, C-2, C-6), 128.2 (CH, C-20, C-60), 127.3 (CH,
JCF = 4.0 Hz, C-3, C-5), 124.8 (JCF = 275 Hz, CF3),
116.2 (CH, C-30, C-50), 45.8 (NH–CH2). Anal. Calcd. for
C16H13N3: C, 45.78; H, 3.12; N, 10.01. Found: C, 45.65; H,
3.32; N, 10.30.
(E)-N-(2-(2-(4-Methoxybenzylidene)hydrazinyl)-2-
oxoethyl)-4-(trifluoromethyl)benzene sulfonamide (5c)
White needles (EtOH) (this compound was prepared by the
reaction of compound 4 and 4-methoxybenzaldehyde. It
was obtained as a white solid); mp 163–165 °C; IR (KBr)
1
mmax 3312, 3158, 3070, 1680, 1634, 1151, 1064 cm-1; H
NMR (DMSO-d6, 400 MHz): d = 9.39 (1H, s, NH), 8.47
(1H, s, N=CH), 8.04 (1H, s, NH), 7.98 (2H, d, H-20, H-60),
7.51–7.72 (4H, m, H-3, H-5, H-30, H-50), 7.06 (2H, dd, H-2,
H-6), 4.58 (2H, s, –CH2), 3.88 (3H, s, –OCH3); 13C NMR
(DMSO-d6, 100 MHz): d = 171.1 (C, C=O), 160.3 (C,
C-40), 149.8 (C, C-1), 144.2 (CH, C=N), 134.2
(JCF = 32.0 Hz, C-4), 130.5 (CH, C-20, C-60), 129.6 (CH,
C-2, C-6), 127.2 (C, C-10), 126.1 (CH, JCF = 34.0 Hz, C-3,
C-5), 124.4 (JCF = 274.2 Hz, CF3), 116.4 (CH, C-30, C-50),
55.7 (O–CH3), 45.7 (NH–CH2); Anal. Calcd. for
C17H16N3: C, 49.15; H, 3.88; N, 10.12. Found: C, 49.25; H,
3.64; N, 10.32.
(E)-N-(2-(2-(4-Bromobenzylidene)hydrazinyl)-2-
oxoethyl)-4-(trifluoromethyl)benzene sulfonamide (5f)
White needles (EtOH) (this compound was prepared by the
reaction of compound 4 and 4-bromobenzaldehyde. It was
obtained as a white solid); mp 148–150 °C; IR (KBr) mmax
3310, 3154, 3070, 1660, 1625, 1150, 1068 cm-1; 1H NMR
(DMSO-d6, 400 MHz) d = 9.29 (1H, s, NH), 8.48 (1H, s,
N=CH), 8.06 (1H, s, NH), 7.96 (2H, d, J = 8.56 Hz, H-30,
H-50), 7.45 (2H, d, J = 8.5 Hz, H-3, H-5), 7.04–7.19 (4H,
m, H-2, H-6, H-20, H-60), 4.59 (2H, s, –CH2); 13C NMR
(DMSO-d6, 100 MHz): d = 171.0 (C, C=O), 149.8 (C,
C-1), 144.0 (CH, C=N), 134.4 (C, JCF = 33.7 Hz, C-4),
132.8 (C, C-10), 131.7 (CH, C-20, C-60), 129.6 (CH, C-2,
C-6), 128.5 (C, C-40), 127.0 (CH, JCF = 4.8 Hz, C-3, C-5),
124.4 (JCF = 271.0 Hz, CF3), 116.9 (CH, C30, C-50), 46.1
(NH–CH2); Anal. Calcd. for C16H13N3: C, 41.39; H, 2.82;
N, 9.05. Found: C, 41.43; H, 2.93; N, 9.24.
(E)-N-(2-(2-(2-Chlorobenzylidene)hydrazinyl)-2-
oxoethyl)-4-(trifluoromethyl)benzene sulfonamide (5d)
Yellow needles (EtOH) (this compound was prepared by
the reaction of compound 4 and 2-chlorobenzaldehyde. It
was obtained as a yellow solid); mp 154–156 °C; IR (KBr)
1
mmax 3303, 3145, 3073, 1681, 1631, 1159, 1050 cm-1; H
(E)-N-(2-(2-(2-Nitrobenzylidene)hydrazinyl)-2-
NMR (DMSO-d6, 400 MHz): d = 9.32 (1H, s, NH), 8.51
(1H, s, N=CH), 8.05 (1H, s, NH), 7.66–7.78 (3H, m, H-3,
H-5, H-60), 7.59 (1H, s, H-30), 7.04–7.12 (4H, m, H-2, H-6,
H-40, H-50), 4.59 (2H, s, –CH2); 13C NMR (DMSO-d6,
100 MHz): d = 171.0 (C, C=O), 144.6 (C, C-1), 140.1
(CH, C=N), 134.4 (C, JCF = 32.6 Hz, C-4), 133.5 (C,
C-20), 132.7 (CH, C-10), 130.4 (CH, C-2, C-6), 127.7 (CH,
oxoethyl)-4-(trifluoromethyl)benzene sulfonamide (5g)
Yellow needles (EtOH) (this compound was prepared by
the reaction of compound 4 and 2-nitrobenzaldehyde. It
was obtained as a yellow solid); mp 164–166 °C; IR (KBr)
mmax 3300, 3150, 3070, 1680, 1630, 1160, 1060 cm-1; H
1
NMR (DMSO-d6, 400 MHz): d = 9.34 (1H, s, NH), 8.46
123

Med Chem Res
(1H, s, N=CH), 8.10–8.15 (1H, m, H-30), 8.08 (1H, s, NH),
7.72–7.85 (5H, m, H-3, H-5, H-40, H-50, H-60), 7.08 (2H,
dd, J = 2.14, 6.8 Hz, H-2, H-6), 4.60 (2H, s, –CH2); 13C
NMR (DMSO-d6, 100 MHz): d = 171.0 (C, C=O), 149.5
(C, C-1), 143.3 (CH, C=N), 135.4 (C, C-20), 134.0 (C,
JCF = 32.6 Hz, C-4), 130.1 (CH, C-50), 128.4 (CH, C-2,
C-6), 128.2 (C, C-10), 128.0 (CH, C-30), 127.0 (CH,
JCF = 4.4 Hz, C-3, C-5), 124.7 (CH, C-60), 124.0
(JCF = 275 Hz, CF3), 45.5 (NH–CH2); Anal. Calcd. for
C16H13N4: C, 44.65; H, 3.04; N, 13.02. Found: C, 44.84; H,
3.14; N, 13.32.
(E)-N-(2-(2-(2,4-Dimethoxybenzylidene)hydrazinyl)-2-
oxoethyl)-4-(trifluoromethyl)benzene sulfonamide (5j)
White needles (EtOH) (this compound was prepared by the
reaction of compound 4 and 2,4-dimethoxybenzaldehyde. It
was obtained as a white solid); mp 173–175 °C; IR (KBr)
mmax 3310, 3144, 3063, 168, 1631, 1156, 1061 cm-1; H
1
NMR (DMSO-d6, 400 MHz): d = 9.39 (1H, s, NH), 8.47
(1H, s, N=CH), 8.04 (1H, s, NH), 7.98 (2H, d, J = 8.64 Hz,
H-1, H-60), 7.51–7.72 (4H, m, H-3, H-5, H-30, H-50), 7.15
(2H, d, J = 5.1 Hz, H-2, H-6), 4.58 (2H, s, –CH2), 3.88 (3H,
s, –OCH3); 13C NMR (DMSO-d6, 100 MHz): d = 171.0 (C,
C=O), 160.2 (C, C-40), 150.0 (C, C-20), 149.2 (C, C-1), 149.0
(CH, C-60), 146.0 (CH, C=N), 134.3 (C, JCF = 32.7 Hz,
C-4), 128.9 (CH, C-2, C-6), 127.2 (CH, JCF = 4.45 Hz, C-3,
C-5), 124.2 (JCF = 273.4 Hz, CF3), 118.2 (CH, C-30), 110.0
(CH, C-50), 52.3 (O-CH3), 45.5 (NH–CH2); Anal. Calcd. for.
C18H18N3: C, 48.54; H, 4.07; N, 9.43. Found: C, 48.74; H,
4.32; N, 9.63.
(E)-N-(2-(2-(4-Fluorobenzylidene)hydrazinyl)-2-oxoethyl)-
4-(trifluoromethyl)benzene sulfonamide (5h)
White needles (EtOH) (this compound was prepared by the
reaction of compound 4 and 4-fluorobenzaldehyde. It was
obtained as a white solid); mp 159–161 °C; IR (KBr) mmax
3306, 3162, 3055, 1670, 1630, 1151, 1061 cm-1; 1H NMR
(DMSO-d6, 400 MHz): d = 9.29 (1H, s, NH). 8.48 (1H, s,
N=CH), 8.09 (1H, s, NH), 7.89 (2H, dd, J = 1.7, 8.70 Hz,
H-20, H-60), 7.22–7.38 (4H, m, H-3, H-5, H-30, H-50), 6.97
(2H, dd, J = 2.11, 6.9 Hz, H-2, H-6), 4.59 (2H, s, –CH2);
13C NMR (DMSO-d6, 100 MHz): d = 171.0 (C, C=O),
166.1 (C, JCF = 238.20 Hz, C-40), 149.2 (C, C-1), 144.0
(CH, C=N), 134.4 (C, JCF = 32.0 Hz, C-4), 130.3 (CH,
C-20, C-60), 130.2 (C, C-10), 128.6 (CH, C-2, C-6), 127.6
(CH, JCF = 4.4 Hz, C-3, C-5), 124.7 (CH, C-60), 124.0
(JCF = 272.0 Hz, CF3), 116.2 (CH, JCF = 9.5 Hz C-30,
C-50), 45.7 (NH–CH2); Anal. Calcd. for C16H13N3: C,
47.64; H, 3.25; N, 10.42. Found: C, 47.81; H, 3.43; N,
10.62.
General procedure for the synthesis of
N-((5-phenyl-1,3,4-oxadiazole-2-yl)methyl)-4-
(trifluoromethyl)benzenesulfonamide (6a–j)
To a stirred solution of 5a–j (0.01 mmol) in dichloro-
methane (10 ml) at room temperature, iodobenzenediace-
tate (0.011 mmol) was added in single lot, and the mixture
was stirred for 1 h. The progress of the reaction was
monitored by TLC. After completion of the reaction, the
reaction mass was concentrated under reduced pressure,
and the solid was isolated with pet ether. The isolated solid
was recrystallized from methanol and dried to yield 2,5-
disubstituted 1,3,4-oxadiazoles 6a–j in 70–92 % yield.
N-((5-Phenyl-1,3,4-oxadiazole-2-yl)methyl)-4-
(E)-N-(2-(2-(3,4-Dichlorobenzylidene)hydrazinyl)-2-
(trifluoromethyl)benzenesulfonamide (6a)
oxoethyl)-4-(trifluoromethyl)benzene.3, sulfonamide (5i)
White needles (MeOH) (this compound was prepared by the
reaction of compound 5a and iodobenzenediacetate. It was
obtained as a white solid); yield 74 %; mp 153–155 °C; IR
(KBr) mmax 3300, 3063, 1680, 1557, 1160, 1061 cm-1; 1H
NMR (DMSO-d6, 400 MHz): d = 8.15 (1H, s, NH), 8.02
(2H, d, J = 8.8 Hz, H-20, H-60), 7.74–7.78 (3H, m, H-30,
H-40, H-50), 7.57 (2H, d, J = 8.46 Hz, H-3, H-5), 7.08 (2H, d,
J = 8.2 Hz, H-2, H-6), 4.60 (2H, s, –CH2); 13C NMR
(DMSO-d6, 100 MHz): d = 164.7 (oxadiazole C-5), 157.8
(oxadiazole C-2), 149.6 (C, C-1), 134.0 (C, JCF = 31.8 Hz,
C-4), 129.5 (CH, C-2, C-6), 128.5 (CH, JCF = 4.44 Hz C-3,
C-5), 128.2 (CH, C-20, C-60), 124.6 (JCF = 270.6 Hz, CF3),
119.4 (C, C-10), 116.2 (CH, C-30, C-50), 115.7 (CH, C-40),
42.1 (CH2, NH–CH2); MS (ESI) m/z: 384.2 [M?1]?; Anal.
Calcd. for C16H12N3: C, 50.13; H, 3.16; N, 10.96. Found: C,
50.00; H, 3.14; N, 10.92.
Off white needles (EtOH) (this compound was prepared by
the reaction of compound 4 and 3,4-dichlorobenzaldehyde.
It was obtained as an off white solid); mp 159–161 °C; IR
(KBr) mmax 3325, 3140, 3062, 1664, 1644, 1158,
1058 cm-1 1H NMR (DMSO-d6, 400 MHz): d = 9.26
;
(1H, s, NH). 8.43 (1H, s, N=CH), 8.09 (1H, s, NH),
7.31–7.34 (1H, t, J = 8.5 Hz, H-50), 7.35–7.42 (4H, m,
H-3, H-5, H-20, H-60), 7.06 (2H, d, J = 8.90 Hz, H-2, H-6),
4.59 (2H, s, –CH2); 13C NMR (DMSO-d6, 100 MHz):
d = 171.1 (C, C=O), 149.6 (C, C-1), 145.8 (CH, C=N),
134.1 (C, JCF = 33.0 Hz, C-4), 133.4 (C, C-10), 130.7 (C,
C-30, C-40), 128.8 (CH, C-2, C-6), 127.6 (CH,
JCF = 4.1 Hz, C-3, C-5), 127.0 (CH, C-50), 125.6 (CH,
C-60), 124.0 (JCF = 274.6 Hz, CF3), 45.5 (NH–CH2);
Anal. Calcd. for C16H12N3: C, 42.31; H, 2.66; N, 9.25.
Found: C, 42.52; H, 2.51; N, 9.35.
123

Med Chem Res
124.9 (JCF = 270.7 Hz, CF3), 124.0 (CH, C-60), 116.2 (C,
C-10), 107.0 (CH, C-50), 41.1(CH2, NH–CH2); MS (ESI) m/z:
419.2 [M?2]?; Anal. Calcd. for C16H11N3 (in %): C, 46.00;
H, 2.65; N, 10.06. Found: C, 46.02; H, 2.69; N, 9.90.
N-((5-(p-Tolyl)-1,3,4-oxadiazole-2-yl)methyl)-4-
(trifluoromethyl)benzenesulfonamide (6b)
White needles (MeOH) (this compound was prepared by the
reaction of compound 5b and iodobenzenediacetate. It was
obtained as a white solid); yield 72 %; mp 171–173 °C; IR
N-((5-(4-Chlorophenyl)-1,3,4-oxadiazole-2-yl)methyl)-4-
(KBr) mmax 3310, 3068, 1670, 1552, 1164, 1066 cm-1; H
1
(trifluoromethyl)benzenesulfonamide (6e)
NMR (DMSO-d6, 400 MHz): d = 8.14 (1H, s, NH),
8.0–8.15 (2H, d, J = 8.5 Hz, H-20, H-60), 7.58 (2H, d,
J = 8.15 Hz, H-3, H-5), 7.35 (4H, m, H2, H-6, H-30, H-50),
4.60 (2H, s, –CH2), 2.18 (3H, s, Ar-CH3); 13C NMR (DMSO-
d6, 100 MHz): d = 164.3 (oxadiazole C-5), 158.8 (oxadi-
azole C-2), 149.6 (C, C-1), 134.0 (C, JCF = 32.3 Hz, C-4),
129.2 (CH, C-2, C-6), 128.9 (CH, JCF = 4.4 Hz, C-3, C-5),
127.0 (CH, C-20, C-60), 124.6 (JCF = 273.6 Hz, CF3), 42.4
(CH2, NH–CH2), 15.3 (CH3, Ar-CH3); MS (ESI) m/z: 398.2
[M?1]?; Anal. Calcd. for C17H14N3: C, 51.38; H, 3.55; N,
10.57. Found: C, 51.35; H, 3.50; N, 10.61.
White needles (MeOH) (this compound was prepared by
the reaction of 5e and iodobenzenediacetate. It was
obtained as a white solid); yield 76 %; mp 181–183 °C; IR
1
(KBr) mmax 3310, 3060, 1680, 1557, 1160, 1061 cm-1; H
NMR (DMSO-d6, 400 MHz): d = 8.14 (s, NH), 8.02 (2H,
d, J = 7.82 Hz, H-20, H-60), 7.74 (2H, d, J = 7.8 Hz, H-30,
H-50), 7.57 (2H, d, J = 8.0 Hz, H-3, H-5), 7.09 (2H, d,
J = 8.1 Hz, H-2, H-6), 4.60 (2H, s, –CH2); 13C NMR
(DMSO-d6, 100 MHz): d = 166.2 (oxadiazole C5), 162.4
(oxadiazole C2), 148.5 (C, C-1), 134.4 (C, JCF = 32.0 Hz,
C-4), 134.0 (C, C-10), 129.4 (CH, C-2, C-6), 128.2 (CH,
JCF = 32.6 Hz, C-3, C-5), 127.3 (CH, C-20, C-60), 124.9
(JCF = 272.8 Hz, CF3), 116.2 (CH, C-30, C-50), 115.6 (C,
C-40), 42.2 (CH2, NH–CH2); MS (ESI) m/z: 419.0 [M?2]?;
Anal. Calcd. for C16H11N3 (in %): C, 46.00; H, 2.65; N,
10.06. Found: C, 46.08; H, 2.62; N, 9.99.
N-((5-(4-Methoxyphenyl)-1,3,4-oxadiazole-2-yl)methyl)-4-
(trifluoromethyl)benzene sulfonamide (6c)
White needles (MeOH) (this compound was prepared by the
reaction of compound 5c and iodobenzenediacetate. It was
obtained as a white solid); yield 79 %; mp 144–146 °C; IR
1
(KBr) mmax 3290, 3048, 1661, 1545, 1154, 1057 cm-1; H
N-((5-(4-Bromophenyl)-1,3,4-oxadiazole-2-yl)methyl)-4-
NMR (DMSO-d6, 400 MHz): d = 8.15 (1H, s, NH), 7.82
(2H, dd, J = 2.0, 8.34 Hz, H-20, H-60), 7.19–7.32 (4H, m,
H-3, H-5, H-30, H-50), 7.06 (2H, dd, J = 1.84, 8.40 Hz, H-2,
H-6), 4.58 (2H, s, –CH2), 3.86 (3H, s, –OCH3); 13C NMR
(DMSO-d6 100 MHz): d = 163.9 (oxadiazole C-5), 161.4
(oxadiazole C-2), 160.2 (C, C-40), 149.8 (C, C-1), 134.0 (C,
JCF = 32.5 Hz, C-4), 129.6 (CH, C-2, C-6), 127.9 (CH,
JCF = 4.13 Hz, C-3, C-5), 124.6 (JCF = 271.8 Hz, CF3),
116.4 (C, C-10), 115.8 (CH, C-20, C-60), 114.4 (CH, C-30,
C-50), 55.6 (CH3, O–CH3), 41.6 (CH2, NH–CH2); MS (ESI)
m/z: 416.2 [M?1]?; Anal. Calcd. for C17H14N3: C, 49.40; H,
3.41; N, 10.17. Found: C, 49.45; H, 3.40; N, 10.10.
(trifluoromethyl)benzenesulfonamide (6f)
White needles (MeOH) (this compound was prepared by
the reaction of 5f and iodobenzenediacetate. It was
obtained as a white solid); yield 78 %; mp 170–172 °C; IR
(KBr) mmax 3320, 3055, 1670, 1550, 1160, 1060 cm-1; H
1
NMR (DMSO-d6, 400 MHz) d: 8.15 (1H, s, NH), 7.94 (2H,
d, J = 8.61 Hz, H-20, H-60), 7.44–7.72 (4H, m, H-3, H-5,
H-30, H-50), 7.05 (2H, d, J = 8.42 Hz, H-2, H-6), 4.60 (2H,
s, –CH2); 13C NMR (DMSO-d6, 100 MHz): d = 165.1
(oxadiazole C5), 163.1 (oxadiazole C2), 149.8 (C, C-1),
134.3 (C, JCF = 32.2 Hz, C-4), 131.7 (CH, C-20, C-60),
129.6 (CH, C-2, C-6), 128.6 (CH, JCF = 4.12 Hz, C-3,
C-5), 127.0 (C, C-10), 123.9 (JCF = 272.2 Hz, CF3), 116.5
(CH, C-30, C-50), 115.2 (C. C-40), 42.2 (CH2, NH–CH2);
MS (ESI) m/z: 461.0 [M?1]?; Anal. Calcd. for
C16H11BrF3N3O3S (in %): C, 41.57; H, 2.40; N, 10.38.
Found: C, 41.50; H, 2.43; N, 10.32.
N-((5-(2-Chlorophenyl)-1,3,4-oxadiazole-2-yl)methyl)-4-
(trifluoromethyl)benzenesulfonamide (6d)
White needles (MeOH) (this compound was prepared by the
reaction of 5d and iodobenzenediacetate. It was obtained as a
white solid); yield 73 %; mp 155–157 °C; IR (KBr) mmax
3300, 3063, 1680, 1557, 1160, 1061 cm-1 1H NMR
;
N-((5-(2-Nitrophenyl)-1,3,4-oxadiazole-2-yl)methyl)-4-
(DMSO-d6, 400 MHz): d = 8.12 (1H, s, NH), 7.76 (2H, d,
J = 8.34 Hz, H-3, H-5), 7.66–7.74 (2H, m, H-30, H-60), 7.04
(4H, m, H-2, H-6, H-40, H-50), 4.59 (2H, s, –CH2); 13C NMR
(DMSO-d6, 100 MHz): d = 164.1 (oxadiazole C5), 163.4
(oxadiazole C2), 149.7 (C, C-1), 134.2 (C, JCF = 32.4 Hz,
C-4), 133.7 (CH, C-20), 130.0 (C, C-40), 129.9 (CH, C-30),
128.6 (CH, C-2, C-6), 127.5 (CH, JCF = 31.7 Hz, C-3, C-5),
(trifluoromethyl)benzenesulfonamide (6g)
White needles (MeOH) (this compound was prepared by
the reaction of 5g and iodobenzenediacetate. It was
obtained as a white solid); yield 73 %; mp 163–165 °C; IR
(KBr) mmax 3290, 3050, 1668, 1564, 1168, 1066 cm-1; 1H
NMR (DMSO-d6, 400 MHz): d = 8.14 (1H, s, NH),
123

Med Chem Res
8.11–8.14 (2H, m, H-30, H-60), 7.76–7.82 (4H, m, H-3, H-5,
H-40, H–50), 7.15 (2H, dd, J = 2.12, 6.90 Hz, H-2, H6),
4.59 (2H, s, –CH2); 13C NMR (DMSO-d6, 100 MHz):
d = 165.1 (oxadiazole C5), 162.5 (oxadiazole C2), 149.5
(C, C-1), 135.4 (C, C-20), 134.0 (C, JCF = 32.2 Hz, C-4),
130.1 (CH, C-50), 129.0 (CH, C-2, C-6), 128.5 (CH,
JCF = 4.11 Hz, C-3, C-5), 124.1 (JCF = 270.9 Hz, CF3),
116.8 (CH, C-40), 115.7, (CH, C-60), 42.4 (CH2, NH–CH2);
MS (ESI) m/z: 429.1 [M?1]?; Anal. Calcd. for C16H11N4
(in %): C, 44.86; H, 2.59; N, 13.08. Found: C, 44.80; H,
2.55; N, 13.00.
N-((5-(2,4-Dimethoxyphenyl)-1,3,4-oxadiazole-2-
yl)methyl)-4-(trifluoromethyl)benzene sulfonamide (6j)
White needles (MeOH) (this compound was prepared by
the reaction of 5j and iodobenzenediacetate. It was
obtained as a white solid); yield 92 %; mp 158–160 °C; IR
(KBr) mmax 3960, 3060, 1680, 1555, 1160, 1060 cm-1; H
1
NMR (DMSO-d6, 400 MHz): d = 8.15 (1H, s, NH),
7.50–7.66 (3H, m, H-3, H-5, H-60), 7.14–7.20 (4H, m, H-2,
H-6, H-30, H-50), 4.59 (2H, s, –CH2), 3.89 (3H, s, –OCH3);
13C NMR (DMSO-d6, 100 MHz): d = 166.6 (oxadiazole
C5), 163.5 (oxadiazole C2), 150.0 (C, C-40), 149.2 (C,
C-20), 149.0 (C, C-1), 134.4 (C, JCF = 32.0 Hz, C-4),
129.0 (CH, C-2, C-6), 128.4 (CH, JCF = 4.12 Hz, C-3,
C-5), 124.1 (JCF = 270.0 Hz, CF3), 118.2 (CH, C-60),
116.2 (C, C-10), 110.0 (CH, C-30), 108.2 (CH, C-50), 52.3
(CH3, O-CH3), 42.1 (CH2, NH–CH2); MS (ESI) m/z: 446.2
[M?1]?; Anal. Calcd. for C18H16N3 (in %): C, 48.76; H,
3.64; N, 9.48. Found: C, 48.79; H, 3.60; N, 9.42.
N-((5-(4-Fluorophenyl)-1,3,4-oxadiazole-2-yl)methyl)-4-
(trifluoromethyl)benzenesulfonamide (6h)
White needles (MeOH) (this compound was prepared by
the reaction of 5h and iodobenzenediacetate. It was
obtained as a white solid); yield 84 %; mp 186–188 °C; IR
(KBr) mmax 3306, 3061, 1670, 1556, 1163, 1062 cm-1; 1
H
NMR (DMSO-d6, 400 MHz): d = 8.14 (1H, s, NH), 7.98
(2H, d, J = 8.55 Hz, H-20, H-60), 7.50 (4H, m, H-3, H-5,
H-30, H-50), 7.11 (2H, dd, J = 2.06, 7.4 Hz, H-2, H-6),
4.60 (2H, s, –CH2); 13C NMR (DMSO-d6, 100 MHz):
d = 165.9 (oxadiazole C5), 163.1 (oxadiazole C2), 166.1
(C, JCF = 239.59 Hz C-40), 149.2 (C, C-1), 134.4 (C,
JCF = 32.0 Hz, C-4), 130.3 (C, C-20, C-60), 129.6 (CH,
C-2, C-6), 129.0 (CH, JCF = 4.0 Hz, C-3, C-5), 124.1
(JCF = 271.8 Hz, CF3), 116.0 (CH, JCF = 9.70 Hz, C-30,
C-50), 115.1 (C, C-10), 42.3 (CH2, NH–CH2); MS (ESI) m/
z: 402.1 [M?1]?; Anal. Calcd. for C16H11N3 (in %): C,
47.88; H, 2.76; N, 10.47. Found: C, 47.89; H, 2.72; N,
10.51.
Antiproliferative activity
The 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium
bromide (MTT) was dissolved (5 mg/ml) in a phosphate
buffer saline (pH 7.2) and filtered before use. The RPMI
1640 cell culture medium, MTT, and fetal bovine serum
(FBS) were purchased from Merck chemicals.
Human metastatic breast cancer (MDA-MB 231),
human chronic myeloid leukemia (K562), human colon
carcinoma (Colo-205), and human neuroblastoma (IMR-
32) cell lines were procured from the National Center for
Cell Sciences in Pune, India. All cells were grown in
RPMI-1640 supplemented with 10 % heat inactivated FBS,
100 IU/ml penicillin, 100 mg/ml streptomycin and 2 mM-
glutamine. The cultures were maintained in a humidified
atmosphere with 5 % CO2 at 37 °C.
N-((5-(3,4-Dichlorophenyl)-1,3,4-oxadiazole-2-yl)methyl)-
4-(trifluoromethyl)benzene sulfonamide (6i)
The potential effects on cell viability were investigated
using the MTT assay (Mallesha et al., 2012). The MTT
assay is an indicator of metabolically active cells. A known
number of MDA-MB 231, K562, Colo-205, and IMR-32
cells were transferred into 96 well plates in a volume of
200 ll of culture medium and incubated for 48 h before the
addition of the test compound. Cells were then exposed to
known concentrations of the compound to be tested
(10 lM expressed as final concentration) for 24 h at 37 °C.
After drug exposure, the culture medium was removed, and
20 ll of MTT reagent (diluted in culture medium, 5 mg/
ml) was added. After incubating for 4 h, the MTT/medium
was removed, and DMSO (100 ll) was added to each well;
the plates were agitated for 1 min. Absorbance of the
colored solution was measured on a multiwell plate reader
(Victor3, Perkin Emler) using a test wavelength of 570 nm.
White needles (MeOH) (this compound was prepared by
the reaction of 5i and iodobenzenediacetate. It was
obtained as a white solid); yield 80 %; mp 173–175 °C; IR
1
(KBr) mmax 3309, 3066, 1674, 1560, 1154, 1069 cm-1; H
NMR (DMSO-d6, 400 MHz) d: 8.15 (1H, s, NH),
7.82–7.84 (2H, m, H-20, H-60), 7.39 (2H, d, J = 8.8 Hz,
H-3, H-5), 7.31 (1H, s, H-50), 7.12 (2H, dd, J = 1.90,
6.80 Hz, H-2, H-6), 4.59 (2H, s, –CH2); 13C NMR (DMSO-
d6, 100 MHz): d = 165.8 (oxadiazole C5), 162.8 (oxadi-
azole C2), 149.6 (C, C-1), 134.1 (C, JCF = 32.47 Hz, C-4),
133.4 (C, C-40), 130.7 (C, C-30), 128.8 (CH, C-2, C-6),
128.5 (CH, JCF = 4.41 Hz, C-3, C-5), 127.0 (CH, C-60),
1256 (C, C-10), 124.2 (JCF = 274.3 Hz, CF3), 116.4 (CH,
C-20), 115.6 (CH, C-50), 42.1 (CH2, NH–CH2); MS (ESI)
m/z: 354.2 [M?2]?; Anal. Calcd. for C16H10N3 (in %): C,
42.49; H, 2.23; N, 9.29. Found: C, 42.45; H, 2.20; N, 9.28.
123

Med Chem Res
Results were evaluated by comparing the absorbance of the
wells containing compound-treated cells with the absor-
bance of wells containing 0.1 % DMSO alone (solvent
control). Conventionally, cell viability was estimated to be
100 % in the solvent control, and the assay was performed
in triplicate.
ethanol as per the reported procedure (Jayashankar et al.,
2009). Compounds 5a–j was prepared by refluxing a
mixture of aldehydes in absolute ethanol for about 2 h. A
series of new compounds (6a–j) have been accomplished in
excellent yields by the oxidation of 5a–j with one equiv-
alents of iodobenzenediacetate (IBD) in dichloromethane.
Compounds 5a–j and 6a–j were synthesized based on
reported procedure (Prakash et al., 2010).
Results and discussion
The FT-IR spectra were recorded using KBr pellets in
the range of 4,000–400 cm-1. The structure of compounds
5a–j was confirmed using IR and 1H NMR. The IR spectra
of the compound 5a exhibited characteristic absorption
bands at 1,631 and 3,150 cm-1 due to carbonyl and NH
Chemistry
The title compounds were prepared using the synthetic
strategy described in Scheme 1. The chemical structures of
the new compounds are given in Table 1. Compound 3 was
synthesized by the reaction of glycine ethyl ester hydro-
chloride 1 with 4-(trifluoromethyl)benzenesulfonyl chlo-
ride 2 in the presence of a base. Compound 4 was
synthesized by the reaction of 3 with hydrazine hydrate in
1
groups, respectively. The H NMR spectra of 5a showed
two singlet due to N=CH and NH at d 8.62 and d 9.35,
respectively. The structures of all compounds 6a–j were
1
confirmed by their spectral (IR, LCMS, H NMR, and 13C
NMR) and elemental analyses. The characterization of
product 6a–j was based upon a careful comparison of their
Scheme 1 Reagent and
reaction conditions: i DCM,
TEA, r.t., 1 h; ii hydrazine
hydrate, reflux, 3 h; iii
substituted benzaldehydes,
EtOH, H?, r.t., 2 h; and iv
iodobenzene diacetate, DCM,
r.t., 1 h
O
O
O
O
O
S
S
O
N
(i)
+
Cl
F
F
H
F
F
H2N
O
F
F
O
HCl
3
2
1
(ii)
O
O
O
S
N
H
F
HN
F
NH2
4
F
(iii)
O
O
O
S
N
H
F
HN
F
N
5(a-j)
F
Ar
(iv)
O
O
S
N
N
H
N
F
F
F
O
Ar
6(a-j)
123

Med Chem Res
Table 1 Chemical structure of 6(a–j)
Compound
Ar
Structure
6a
6b
6c
6d
6e
6f
Phenyl
N
N
N
N
O
S
H
N
O
O
F
F
F
4-Methylphenyl
4-Methoxylphenyl
2-Chlorophenyl
4-Chlorophenyl
4-Bromophenyl
2-Nitrophenyl
N
CH3
O
S
H
N
O
O
F
F
F
N
OCH3
O
S
H
N
O
O
F
F
F
Cl
N
N
N
O
S
H
N
O
O
F
F
F
N
Cl
Br
O
S
H
N
O
O
F
F
F
N
N
O
S
H
N
O
O
F
F
F
O2N
6g
N
N
O
S
H
N
O
O
F
F
F
123

Med Chem Res
Table 1 continued
Compound
Ar
Structure
6h
4-Fluorophenyl
N
N
F
O
S
H
O
N
O
F
F
F
Cl
6i
3,4-Dichlorophenyl
N
N
N
Cl
O H
O
N
S
O
F
H3CO
F
6j
2,4-Methoxyphenyl
F
N
OCH3
O H
O
N
S
O
F
F
F
1
IR and H NMR spectra with those of 5a–j. For example,
IR spectra of 6a were found to be transparent in the region
of NH stretch and CO stretch. In 1H NMR spectra of 6a–j,
the disappearance of their singlet due to N=CH around d
8.4–8.6 and NH proton around d 9.3–9.5, thus, confirming
the oxidation of 5a–j into 6a–j. 13C NMR spectra present
the correct number of carbon atoms at the appropriate
chemical shift values. The mass spectra of 6a showed
molecular ion peak at m/z 384.2 which is in agreement with
the molecular formula C16H12F3N3O3S. The elemental
analyses data showed good agreement between the exper-
imentally determined values and the theoretically calcu-
lated values within 0.4 %.
blue formazan product which is quantifiable spectropho-
tometrically. The percentage cell survival for tested com-
pounds against MDA-MB 231, K562, Colo-205, and IMR-
32 cells is tabulated in Table 2. The extent of inhibition of
cell lines by 6h and 6i is schematically presented in Fig. 1.
The results were expressed as percentage of cell prolifer-
ation compared with cells in control (cells treated with
vehicle, 0.1 % DMSO).
Table 2 Antiproliferative activity of 6a–j against human cancer cells
determined using MTT test
Compound
% Cell survival at 10 lM
K562 Colo-205 MDA-MB 231 IMR-32
In vitro antiproliferative activity
a
6a
6b
6c
6d
6e
6f
–
–
–
50.28
48.50
47.10
50.04
47.50
46.20
57.50
57.47
51.40
53.00
62.40
60.05
40.68
48.70
47.33
47.15
55.40
54.39
50.31
51.20
68.22
60.81
41.50
a
a
Antiproliferative activity of 1,3,4-oxadiazoles against
human neuroblastoma (IMR-32) cell lines (Gudipati et al.,
2011) has been reported. A new class of sulfonamides has
been used in the treatment of diseases arising from
abnormal cell growth and proliferation (Shan et al., 1999).
The antiproliferative action of the synthesized compounds
6a–j was tested against four different cell lines. The
activity was evaluated by measuring the levels of surviving
cells after incubation for 24 h with the test samples using
the MTT colorimetric assay based on the ability of meta-
bolically active cells to convert the pale yellow MTT to a
45.51 60.01
45.50 60.10
42.00 52.20
43.22 55.32
59.31 64.00
6g
6h
6i
48.20 61.70
a
–
6j
42.52
100
Control (0.1 % DMSO) 100
100
100
a
Represents \30 % cell survival
123

Med Chem Res
in vitro. The additional modification and diversification of
functional groups in order to improve the anticancer
activity is currently in progress.
Acknowledgments The authors thank Ravi Alvala, Department of
Pharmacology and Toxicology, G Pullareddy College of Pharmacy,
Hyderabad, India to carryout activity. One of the authors (B. N. Pra-
sanna Kumar) grateful to Synzene International Private Limited,
Bangalore, India, to carryout higher education.
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