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AHSAN/Turk J Chem
2. Results and discussion
2.1. Chemistry
As shown in the Scheme, ethyl(2,4-dichlorophenoxy)acetate (3) was synthesized by stirring a mixture of 2,4-
18,19
dichlorphenol (1) and ethylchloroacetate (2) suspended in acetone and potassium carbonate for 24 h.
Ethyl(2,4-dichlorophenoxy)acetate (3) was further refluxed with hydrazine hydrate in ethanol for 6 h to syn-
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thesize 2-(2,4-dichlorophenoxy)acetohydrazide (4).
In the final step, an equimolar quantity of 2-(2,4-
dichlorophenoxy)acetohydrazide (4) and aromatic aldehyde was refluxed in an ethanol/water system (1:2, v/v)
solvent by adding 20 mol% NaHSO3 for 10 h to obtain 2-[(2,4-dichlorophenoxy)methyl]-5-aryl-1,3,4-oxadiazole
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(5a–h). The progress of the reaction was monitored throughout by thin-layer chromatography (TLC) using
n-hexane:ethylacetate (1:1) as mobile phase. Base-catalyzed synthesis of 3-[(2,4-dichlorophenoxy)methyl]-5-
aryl-4H -1,2,4-triazole (5i,j) was achieved by refluxing 2-(2,4-dichlorophenoxy)acetohydrazide (4) and nitrile in
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n-butanol for 2–3 h in the presence of K2 CO3 . The progress of the reactions was monitored throughout
by TLC (Silica gel 60 F254) using mobile phase, chloroform–methanol (9:1), and benzene–acetone (9:1). The
spots were visualized under either iodine vapor or UV light. All the compounds were obtained in satisfactory
yield ranging between 52% and 81%. All the chemicals were procured from CDH (New Delhi, India), Merck
(Kenilworth, NJ, USA), and SD Fine (Mumbai, India). The title compounds (5a–j) were further characterized
1
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by infrared (IR), nuclear magnetic resonance ( H NMR and C NMR), and mass spectral data. IR, NMR, and
mass spectra data were obtained on a Shimadzu 8201 PC (Kyoto, Japan), Bruker AC 400 MHz spectrometer (in
DMSO-d6) (Billerica, MA, USA), and Bruker Esquire LCMS using ESI, respectively. The purity of compounds
1
was checked by elemental analyses (PerkinElmer 2400 elemental analyzer, Waltham, MA, USA). In the
H
NMR, the prototype compound 5e showed a singlet at δ 5.27 ppm corresponding to the protons of CH2 , a
doublet at δ 6.85 ppm corresponding to one aromatic proton, a double doublet at δ 7.11 ppm corresponding
to another aromatic proton of 2,4-dichlorophenyl, a multiplet at δ 7.23–7.70 ppm corresponding to the four
aromatic protons, a singlet at δ 8.31 ppm corresponding to the one aromatic proton (2,4-dichlorophenyl), and
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a singlet at δ 10.03 ppm corresponding to the phenolic proton (ArOH). The C NMR of compound 5e showed
δ ppm: 166.52, 155.61, 152.83, 142.18, 131.49, 130.51, 128.91, 128.20, 128.13, 124.09, 121.99, 117.17, 116.31,
+
+
112.22, and 67.0. The mass spectra showed (M+H) and (M+2) at 337 and 338, respectively.
3. Cytotoxicity
All the title compounds (5a–j) were evaluated for their cytotoxicity at 10 µM drug concentrations as per the
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National Cancer Institute (NCI) protocol on nine different panels of 59 human cancer cell lines.
The results
of cytotoxicity study are given in Table 1. All the tested compounds showed moderate or weaker cytotoxicity
except for 5e, which showed promising cytotoxicity among the series. The compounds 5a, 5b, 5f, and 5g
showed higher sensitivity towards the UACC 257 (melanoma) [percent growth inhibitions (%GIs) = 43.11,
28.58, 45.05, and 40.58, respectively], NCI-H522 (non-small cell lung cancer) (%GIs = 39.29, 39.28, 36.14,
and 40.83, respectively) and A549/ATCC (non-small cell lung cancer) (%GIs = 29.97, 23.44, 20.45, and 28.05,
respectively). Compounds 5i and 5j showed higher sensitivity towards the UO-31 (renal cancer) with %GIs of
22.89 and 23.43, respectively. Similarly, compounds 5e and 5h showed higher sensitivity towards the NCI-H522
(non-small cell lung cancer) with %GIs of 98.03 and 36.89. Overall, excellent growth control (%GI of 98.03)
regarding NCI-H522 (non-small cell lung cancer) was observed in compound 5e. Compounds with GIs of ≥68%
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