494 Letters in Drug Design & Discovery, 2011, Vol. 8, No. 5
Al-kahraman et al.
(Table 2). Contd…..
No.
4l
IR (KBr, cm-1)
1H NMR (CDCl3 , ꢀ ppm)
13C NMR (CDCl3, ꢀ ppm)
3295 (N-H),
1705 (C=O),
1620 (C=N)
9.80, (bs, 1H, NH, D2O exchangeable), 7.45-7.20 (m, 6H, arom),
6.92 (dd, 2H, arom), 4.05 (q, 2H, methylene), 1.45 (t, 3H, methyl).
164.0, 158.5, 155.5, 147.9, 145.2, 131.8, 129.2,
124.5, 122.3, 121.5, 117.4, 115.2, 63.5, 14.2.
4m
4n
9.85, (bs, 1H, NH, D2O exchangeable), 7.48-7.22 (m, 8H, arom).
3295 (N-H),
1705 (C=O),
1605 (C=N)
164.3, 158.9, 151.9, 148.8, 146.4, 131.2, 129.7,
125.3, 123.4, 122.2, 121.7, 118.2.
3285 (N-H),
1705 (C=O),
1610 (C=N)
10.15, (bs, 1H, NH, D2O exchangeable), 7.64-7.23 (m, 11H,
arom).
164.5, 158.6, 150.2, 147.9, 135.5, 131.3, 129.8,
128.2, 127.8, 127.5, 126.8, 126.3, 124.5, 121.7,
117.8, 115.2
o
zhydrylamine 4e was slightly inferior in activity (IC50 = 0.63
μg/ml)) than the N-aryl imine, N-(2-hydroxybenzylidene)
aniline 4f (IC50 = 0.58 μg/ml). All three N-non-aryl imines of
indoline-2,3-diones 4i-k showed better activity to N-aryl
imines 4l-n with exception of 3-(4-nitrophenyl)iminoindolin-
2-one 4n which was the most active in the series (IC50 = 0.59
μg/ml). Although the N-alkyl imines appeared superior to N-
aryl imines, the effect of substituents in all three classes was
not the same indicating the different factors operating in
compound – microorganism interaction of the three classes
of imines.
cillin and streptomycin, respectively at 24 C in a shaking
incubator [14].
Each compound to be tested and amphotericin B (as a
positive control) were dissolved in DMSO to a concentration
of 1 mg/ml. Parasites at log phase were centrifuged at 3000
rpm for 3 min. Parasites were diluted in fresh culture me-
dium to a final density of 2 x106 cells/ml. In 96-well plates,
180 μl of medium was added in different wells. Experimen-
tal compound (20 μl) was added in medium and serially di-
luted. Parasite culture (100 μl) was added in all wells. In
negative controls, DMSO was serially diluted in medium
while the positive control contained varying concentrations
of standard antileishmanial compound i.e. amphotericin B.
3. EXPERIMENTAL
3.1. Chemistry
o
The plates were incubated for 72 hours at 24 C. The culture
was examined microscopically on an improved Neubauer
counting chamber and IC50 values of compounds possessing
antileishmanial activity were calculated. All the assays were
run in duplicate. IC50 of samples was determined by using
the Prism software.
Melting points have been recorded on a Stuart Scientific
melting point apparatus and are uncorrected. The IR spectra
were recorded on a Perkin-Elmer-781 IR spectrophotometer
using KBr disc of the sample. The NMR spectra were re-
corded on a Jeol FX 90Q spectrometer using TMS as an in-
ternal standard.
ACKNOWLEDGEMENTS
Thiophene-2-carbaldehyde, 2-hydroxybenzaldehyde, in-
doline-2,3-dione, and all the amines were Aldrich products.
Authors are grateful to the Chemistry Department, Uni-
versity of Botswana, Institute of Biochemistry, University of
Balochistan, and Higher Education Commission (HEC), Is-
lamabad, Pakistan, for providing the necessary research fa-
cilities.
Preparation of Imines: Method A
Salicylaldehyde (1 mmol, 0.12 g) or thiophene-2-
carbaldehyde (0.11 g, 1 mmol) was taken in a 50 ml conical
flask. An equimolar amount of appropriate amine was added
drop-wise to it. A solid was formed within a few minutes
that was recrystallized from ethanol. Imines 4a and 4e-h
were prepared by this method.
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Preparation of Imines: Method B
Thiophene-2-carbaldehyde (0.11 g, 1 mmol) or indolin-
2,3-dione was refluxed with appropriate amine in minimum
amount of ethanol for 2-3 hrs. The completion of the reac-
tion was checked by TLC in each case. After completion of
the reaction, the solvent was evaporated under reduced pres-
sure and the solid product obtained was recrystallized from
ethanol. Imines 4b-d and 4i-n were prepared using this
method.
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[7]
Al-Kahraman, Yasser M.S.A.
