Novel Schiff bases derived from isothiocyanates: synthesis, characterization, and antioxidant activity

Article abstract of DOI:10.1007/s11164-020-04185-w

A series of novel thiosemicarbazones including Schiff bases were synthesized by treatment of various aryl-substituted aldehydes with thiosemicarbazides in ethanol containing one drop of hydrochloric acid at reflux for 3–5 h. For this, thiosemicarbazides were obtained from hydrazine monohydrate and isothiocyanates in cold dry ethanol at 0 °C for 1 h. FT-IR, ¹H NMR, ¹³C NMR, and LC–MS/MS spectroscopic methods and elemental analysis were used to characterize the identification of the synthesized products. The in vitro antioxidant activity of these compounds was tested by the 1,1-diphenyl-2-picryl hydrazyl (DPPH) free radical trapping method. All of the synthesized compounds showed lower antioxidant activity than the ascorbic acid standard and followed the sequence I > VII > X > VI > IV > IX > XI > II > V > III > VIII.

Full text of DOI:10.1007/s11164-020-04185-w

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-020-04185-w
Novel Schif bases derived ꢀrom isothiocyanates: synthesis,
characterization, and antioxidant activity
Hasan Yakan1
Received: 8 April 2020 / Accepted: 11 June 2020
©
Springer Nature B.V. 2020
Abstract
A series of novel thiosemicarbazones including Schiꢀ bases were synthesized by
treatment of various aryl-substituted aldehydes with thiosemicarbazides in ethanol
containing one drop of hydrochloric acid at reꢁux for 3–5 h. For this, thiosemicar-
bazides were obtained from hydrazine monohydrate and isothiocyanates in cold dry
1
13
ethanol at 0 °C for 1 h. FT-IR, H NMR, C NMR, and LC–MS/MS spectroscopic
methods and elemental analysis were used to characterize the identiꢂcation of the
synthesized products. The in vitro antioxidant activity of these compounds was
tested by the 1,1-diphenyl-2-picryl hydrazyl (DPPH) free radical trapping method.
All of the synthesized compounds showed lower antioxidant activity than the ascor-
bic acid standard and followed the sequence I>VII>X>VI>IV>IX>XI>II>
V>III>VIII.
Keywords Schiꢀ bases · Isothiocyanates · Thiosemicarbohydrazides · Antioxidant
activity · Spectroscopic elucidation
Introduction
Schiꢀ bases are a signiꢂcant class of organic and inorganic chemistry, which have
–
CH=N– bond. Schiꢀ bases have shown an extensive spectrum of biological activi-
ties and medicinal properties such as antibacterial [1], antimicrobial [2], antifungal
[3, 4], antioxidant [5, 6], antiviral [3, 7], anti-HIV [8], antitubercular [9], anticancer
10], antiinꢁammatory agents [11], and anticonvulsant [12] activity.
[
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s1116
-020-04185-w) contains supplementary material, which is available to authorized users.
4
*
Hasan Yakan
hasany@omu.edu.tr
1
Department of Mathematics and Science Education, Faculty of Education, Ondokuz Mayıs
University, Samsun, Turkey
Vol.:(012
1
3456789)
3

H. Yakan
Compounds with the structure of –NH–C(=S)NH–N= are known as thiosemi-
carbazones, which are important class of compounds in chemistry, biological, and
pharmaceutical ꢂeld. Thiosemicarbazones have showed biological and medicinal
applications including antimicrobial [13], antifungal [14], antibacterial [14, 15],
antioxidant [16–18], anti-HIV [19], anticonvulsant [13, 20], antiviral [21], antituber-
culosis [22], anticancer [23], enzymatic inhibition [14, 24], and cytotoxicity [13, 14]
properties.
The importance of free radicals and reactive oxygen species (ROS) in the path-
ogenicity of diverse diseases such as inꢁammatory, metabolic disorders, cellular
aging, reperfusion damage, and cancer has attracted considerable attention [25, 26].
Therefore, antioxidants have been reported to play an important role in protecting
humans against many mortal diseases.
In view of these proofs, thiosemicarbazones including Schiꢀ bases are signiꢂcant
which not only possess biological activities, but also in medicinal applications. In
this paper, a new series of novel thiosemicarbazones including Schiꢀ bases were
synthesized. The chemical structure of the products was characterized by using
1
13
methods FT-IR, H NMR, C NMR, and LC–MS/MS spectroscopy and elemental
analysis. These compounds were performed antioxidant activity in vitro by using
DPPH free radical scavenging method.
Experimental section
Instruments and reagents
All the chemical materials were bought in Sigma-Aldrich or Merck Chemical Com-
pany and were used without further puriꢂcation. The solvent was spectroscopic
grade. Melting points were measured using a Stuart SMP 30 melting point appara-
tus and were uncorrected. The elemental analysis was performed on a Eurovector
EA3000-Single. Infrared spectra were recorded on a Bruker Alpha FT-IR spectrom-
1
13
eter. H NMR and C NMR spectra (in DMSO-d ) were taken at 25 °C using a
6
Bruker Avance DPX-400 spectrometer operating at 400 MHz and 100 MHz, respec-
tively. The splitting patterns are indicated as s (singlet), d (doublet), dd (doublet
of doublets), t (triplet), q (quartet), and m (multiplied). Absorption measurements
were recorded with a Shimadzu UVM-1240 UV–visible spectrophotometer. Liquid
chromatography—tandem mass spectrometry (LC–MS/MS) measurements were
recorded with a Shimadzu LCMS-8030 Plus spectrophotometer.
Synthesis of novel thiosemicarbazones including Schiꢀ bases (I–XI)
Thiosemicarbazides (0.6 mmol), various aryl-substituted aldehydes (0.6 mmol),
and one drop of HCl were added to aqueous EtOH (30 mL), and the mixture was
reꢁuxed at 78 °C for 3–5 h. The obtained precipitate was ꢂltered and washed, and
then, the formed colored solid was isolated and dried in air. The products were
obtained good yields (63–83%) as shown in Scheme 1.
1
3

Novel Schif bases derived ꢀrom isothiocyanates: synthesis,…
Scheme 1 Synthetic path for the novel thiosemicarbazones including Schiꢀ bases (I–XI)
Antioxidant activity measurements by using DPPH method
The DPPH method is a method showing that the ability of compounds to lose
hydrogen and structurally stable radicals is associated with higher cleaning activ-
ity of the molecule.
Antioxidant activity determinations of compounds synthesized using DPPH
free radical cleaning method were performed. For this, Brand-Williams et al. [27]
method implementation was used with minor changes. The stock solutions of the
synthesized compounds were prepared to be 250 µM in DMSO and mixed with 3
mL DPPH (250 µM) solution in diꢀerent volumes (10–200 µL). Suꢃcient etha-
nol was added until the total solution volume was 5 mL. The prepared mixtures
were kept in a dark room for 30 min and read against the blanks to compare with
a sample without sample at 517 nm. Antioxidant activity was calculated using the
equation shown below as a percentage of inhibition [28]:
ꢀ
ꢁ
ꢂ
ꢃ
(
%) inhibition = A − A ∕A × 100
0 1 0
Here, A is the absorbance of the control (empty, without compound) and A is
0
1
the absorbance of the compound. With the help of the inhibition values obtained,
IC (µM) values were calculated and used to evaluate antioxidant activity [29].
5
0
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H. Yakan
Results and discussion
Physical data
All the synthesized compounds are new. In Table 1, the physical data, melting
points, yields, LC–MS/MS results, and elemental analysis of these compounds are
presented.
Vibrational frequencies
In the FT-IR spectra, the signal of the aldehyde group (–CHO, two bands) of the
–
1
starting material was not observed at 2780–2660 cm . Moreover, the symmetric and
asymmetric stretching bands of the amino group (–NH ) did not show at 3520–3250
2
–
1
cm . Instead, new absorptions for the –C=N stretching bands of imine group were
−1
observed at 1599–1522 cm . These results indicated a successful reaction, as
expected. For all compounds (I–XI), the –OH stretching vibrations were observed
–
1
in the range of 3574–3376 cm , the amino group (=N–NH and –NH–Ar) stretch-
−
1
ing vibrations were observed in the range of 3395–3284 and 3299–3116 cm ,
aromatic and aliphatic C–H stretching vibrations were observed in the range of
−1
3
168–3017 and 2995–2962 cm , –C=N characteristic absorptions of imine group
−1
were observed between 1595 and 1539 cm , the –C=S signal of semicarbazide
−
1
region was observed in the range of 1474–1352 cm , the –C–N group absorptions
−1
were observed at 1333–1207 cm , the –C–O stretching vibration was appeared in
−1
the range of 1222–1094 cm , and the Ar–F stretching vibration was appeared at
−1
1
172–1044 cm , except for compounds X and XI. Ar–Br absorption bands of com-
−1
pounds III and IX were observed at 629 and 591 cm (see Figures S7 and S22 in
supplementary material).
–
1
In compound IV, the –OH stretching vibration was observed at 3574 cm ,
−
1
while the =N–NH (amino) stretching vibration was observed at 3308 cm ; the
−
1
–
NH–Ar (amino) stretching vibration was observed at 3145 cm . The –C=N
−1
stretching vibration was observed at 1592 cm ; the –C=S signal of semicarbazide
−1
region was observed at 1434 cm ; the –C–N stretching vibration was appeared at
−1
−1
1
277 cm ; the –C–O stretching vibration was appeared at 1220 cm ; the –C–F
−1
stretching vibration was appeared at 1067 cm as shown in Fig. 1. These values
provided signiꢂcant proofs for the products formation. IR values of all compounds
are listed in Table 2, and spectra of them are given in supplementary material. These
observations are consistent with values published formerly for similar compounds
[
17, 18, 30, 31].
1
Interpretation of the H NMR spectra
1
The H NMR spectra of the synthesized compounds were detected in DMSO-d
6
as solvent. For compounds I–IX, the –NH peak (=N–NH) was observed as a sin-
glet at 11.97–11.72 ppm, and the –NH signal (–NH–Ar) was detected as a singlet
1
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Novel Schif bases derived ꢀrom isothiocyanates: synthesis,…
1
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H. Yakan
Fig. 1 IR spectrum of compound IV
Table 2 FT-IR values of the compounds (cm−1
)
Compound
OH
=N–NH
–NH–Ar
C=N
C=S
C–N
C–O
C–F
I
3554
3465
3376
3574
3378
3527
3494
3489
3517
3525
3446
3395
3323
3285
3308
3284
3292
3290
3378
3289
3363
3318
3299
3148
3116
3145
3156
3135
3145
3141
3146
3150
3171
1595
1575
1539
1592
1583
1589
1592
1562
1592
1552
1547
1405
1400
1474
1434
1447
1458
1427
1461
1427
1375
1352
1213
1272
1281
1277
1270
1221
1265
1263
1333
1298
1207
1173
1220
1097
1220
1144
1094
1222
1195
1222
1112
1120
1140
1134
1048
1067
1073
1044
1172
1078
1172
–
II
III
IV
V
VI
VII
VIII
IX
X
XI
–
at 11.40–9.82 ppm. The signal of imine (–CH=N) was observed as a singlet at
1
0.24–8.03 ppm. The –OH proton signal was observed as a singlet in the range
1
of 10.36–9.06 ppm. In H NMR spectrum of compound IV, while the –NH peak
(
=N–NH) was observed as a singlet at 11.79 ppm, the –NH signal (–NH–Ar) was
detected as a singlet at 10.05 ppm. The signal of imine (–CH=N) was observed as
a singlet at 8.08 ppm. The –OH (H1) proton signal was observed as a singlet in the
range of 9.96 ppm as shown in Fig. 2. The H2 and H5 proton coupled to the H3 and
H4 proton and detected doublet peaks at 6.83–6.81 ppm, respectively. The H3 and
H4 proton coupled to the H2 and H5 proton and detected doublet peaks at 7.75–7.72
1
3

Novel Schif bases derived ꢀrom isothiocyanates: synthesis,…
Fig. 2 1H NMR spectrum of compound IV
ppm, respectively. The H6 proton coupled to the H7 proton and was observed as
a doublet peak at 7.66–7.63 ppm. The H7 proton coupled to the H6 and H8 pro-
ton showed doublet of doublets peaks at 7.49–7.47 ppm. The H8 proton coupled to
the H6, H7, and H8 proton showed doublets of triplet peaks at 7.05–6.99 ppm. The
H9 proton coupled to the H7 and H8 proton showed doublet of doublets peaks at
7
.42–7.36 ppm. Additionally, while the proton atoms of ethoxy (–OCH CH ) group
2 3
were detected around at 4.11–4.06 (quartet, 2H) and 1.37–1.32 (triplet, 3H) ppm
for compounds I, VI, and X, the methoxy (–OCH ) signal was observed as a singlet
3
peak around at 3.83 ppm for compounds II, VII, IX, and XI as shown in Table 3
(
see also Figs. 5, 17, 20, and 29). In compounds I, VI, and X, the CH proton of
3
ethoxy coupled to OCH protons showed as triplet peaks at 1.37–1.32 ppm, whereas
2
CH proton of ethoxy coupled to CH protons was resonated as quartet peaks at
2
3
4
.11–4.06 ppm (see Figures S2, S14, and S26 in supplementary material). The pro-
ton of CH coupled to NH proton was detected as doublet peaks at 3.03–3.02 and
3
3
8
.01–2.99 ppm, whereas NH proton coupled to CH protons showed quartet peaks at
3
.37–8.36 and 8.40–8.38 ppm for compounds X and XI (see Figures S26 and S29 in
supplementary material). DMSO-d and water in DMSO (HOD, H O) signals were
6
2
shown about at 2.00, 2.50 (quintet), and 3.30 (variable, depending on the solvent and
its concentration) ppm, respectively [32]. These data are in agreement with the val-
ues of previously reported for similar compounds [17, 18, 30, 31]. It is apparent that
structure of the obtained compounds and electronic eꢀects of groups/substituents in
structures plays a signiꢂcant role to chemical shift value. Electron-donating groups
(
OH, NH , OCH , CH , etc.) and electron-withdrawing groups (NO , CN, CF ,
2
3
3
2
3
1
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H. Yakan
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3

Novel Schif bases derived ꢀrom isothiocyanates: synthesis,…
1
3

H. Yakan
1
3

Novel Schif bases derived ꢀrom isothiocyanates: synthesis,…
F, Cl, Br, etc.) have aꢀected chemical shift value with mesomeric (or resonance),
inductive eꢀect [33]. Moreover, the position of these groups/substituents in the mol-
ecules plays a major role as well. Proton chemical shift values of the synthesized
1
compounds are given in Table 3. Moreover, all tested compounds’ IR, H NMR, and
1
3
C NMR spectra were given in supplementary material (Figures S1–S30).
13
Interpretation of the C NMR spectra
1
3
The C NMR spectra of all compounds were obtained in DMSO-d as solvent.
6
1
3
The C NMR spectrum of the compound IV showed 14 diꢀerent resonances in
good agreement with the proposed structure as shown in Fig. 3. For compounds
I–XI, the –C=S (C8) signals of the thiosemicarbohydrazide region were detected
between 177.9 and 175.2 ppm, and the –C=N peaks were observed in the range
of 144.6–138.5 ppm. In compounds I–V, the C11 carbon atoms were detected at
1
63.3–160.1 ppm, shifted downꢂeld (high values, δ) due to the presence of ꢁuo-
rine atom (m-F) (see Figures S3, S6, S9, and S12 in supplementary material). The
C10 carbon atoms were detected at 161.2–156.6 ppm, shifted downꢂeld (high val-
ues, δ) due to the presence of ꢁuorine atom (o-F) for compounds VI–IX. Further-
more, the C9–C14 atoms were also split into doublets due to interacting with the
atomic nucleus of F except for compounds X and XI. The C1 carbon atoms were
observed at 147.6–163.2 ppm, shifted downꢂeld (high values, δ) due to the presence
of hydroxyl or methoxy group (–OH or –OCH ) except for compounds III–VIII.
3
Fig. 3 13C NMR spectrum of compound IV
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H. Yakan
The C2 carbon atoms were observed at 147.1–149.9 ppm, shifted downꢂeld (high
values, δ) due to the presence of hydroxyl, methoxy, or ethoxy group (–OH, –OCH ,
3
or –OC H ) except for compounds III–V, VIII. The C3 carbon atoms were observed
2
5
at 156.4, 158.8, and 156.3 ppm, shifted downꢂeld (high values, δ) due to the pres-
ence of hydroxyl group (–OH) for compounds III, V, and VIII, respectively (see
Figures S9, S12 and S21 in supplementary material).
1
In H NMR spectrum of compound IV, the characteristic –C=N (C7) peak
was observed at 144.3 ppm; the –C=S (C8) signal of the thiosemicarbohydrazide
region was detected at 175.6 ppm. The carbons (C1–C6) of the aldehyde ring were
observed at 163.2, 116.0, 130.0, 125.3, 130.0, and 116.0 ppm, respectively. The C1
carbon atom resonated downꢂeld (high value, δ) due to the presence of hydroxy
(
–OH) group. Moreover, equivalent-symmetry carbon atoms (C2 with C6, C3 with
C5) had the same chemical environment and gave the same signal. The aromatic
carbons (C9–C14) of aryl-thiosemicarbohydrazone ring were observed at between
1
1
41.4 and 111.9 ppm. The aromatic carbons (C9–C14) were observed at 141.4,
41.3; 112.5, 112.3; 160.8, 160.1; 112.1, 111.9; 129.9, 129.8; 121.5; and 121.4
ppm, respectively. The C11 (160.8, 160.1 ppm) carbon atom was shifted downꢂeld
(
high values, δ) due to the presence of ꢁuorine atom. Additionally, while the carbon
atoms of ethoxy (–OCH CH ) group were detected around at 64.5 and 15.2 ppm for
2
3
compounds I, VI, and X, the methoxy (–OCH ) signal was observed around at 56.3
3
ppm for compounds II, VII, IX, and XI. These results are suitable with the values
published previously for similar compounds [17, 18, 30, 31]. The carbon chemical
shift values of the synthesized compounds are given in Table 4 (see also supplemen-
tary material).
Evaluation of antioxidant activity
Ascorbic acid was used as standard for antioxidant activity evaluations. Inhibition
percentages of ascorbic acid and synthesized compounds calculated against concen-
tration are given in Fig. 4.
In this study, antioxidant inhibition percentages for the 11 diꢀerent molecules
we synthesized showed a regular increase in direct proportion to the increase in
concentration. Among them, especially compounds I, VII, and X, although low
against standard antioxidants, exhibited the highest inhibition rates among other
compounds. Compound VI showed a lower percent inhibition in the concentration
ranges of (0.5–2.5) µM, but showed a lower increase in concentrations of 5–10 µM
and showed a stable state in percent inhibition. IC values were also calculated to
5
0
evaluate antioxidant activities. In this study, IC values for ascorbic acid and com-
5
0
pound are summarized in Table 5. Accordingly, the calculated IC value for ascor-
5
0
bic acid was 10.50± 0.01 µM. IC values for the newly synthesized compounds fol-
5
0
lowed the order I>VII>X>VI>IV>IX>XI>II>V>III>VIII.
It is possible to compare free radical scavenging activity between diꢀer-
ent molecules by knowing that antioxidant activity is inversely proportional to
increase in IC values. According to these results, p-hydroxybenzaldehyde-
5
0
derived compounds containing methoxy and ethoxy groups at diꢀerent positions
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Novel Schif bases derived ꢀrom isothiocyanates: synthesis,…
1
3

H. Yakan
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3

Novel Schif bases derived ꢀrom isothiocyanates: synthesis,…
30
25
20
15
10
5
0
I
II
III
IV
V
VI
VII
VIII
IX
X
XI
Ascorbic Acid
0
.5
1
2.5
5
10
Concentration (µM)
Fig. 4 Percentage change of inhibition calculated by DPPH method for ascorbic acid and synthesized
compounds
Table 5 IC values for the
5
0
Compounds
DPPH scavenging
activity IC50 (μM)a
synthesized compounds
I
19.24± 0.01
118.06± 0.09
146.51± 0.16
53.17± 0.05
123.05± 0.15
42.32± 0.03
26.04± 0.02
191.06± 0.23
53.19± 0.05
29.99± 0.01
84.96± 0.12
16.50± 0.01
II
III
IV
V
VI
VII
VIII
IX
X
XI
Ascorbic acid
Values are expressed as means (n=3)
a
IC =the concentration (μM) exhibiting 50% inhibition of DPPH
5
0
radical
showed the highest antioxidant activity. However, synthesized structures (III and
VIII) possessing bromine atom exhibited lower antioxidant activity. Furthermore,
as Muğlu et al. [34] mentioned in their study, the presence of thio group is eꢀec-
tive in showing antioxidant properties of compounds. In particular as mentioned
in the studies of Bakır and Lawag [5], the presence of electron-donating methoxy
and ethoxy structures in the compounds containing phenolic structure (I, VII,
X, VI, IX, XI, II) contributed to the increase in the antioxidant activity of the
compound.
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H. Yakan
Conclusions
In this paper, novel thiosemicarbazones including Schiꢀ bases have been prepared
with good yields of 63–83%. All the products were characterized by methods with
1
13
FT-IR, H NMR, C NMR, and LC–MS/MS spectroscopy and elemental analy-
ses. The in vitro antioxidant activity of the synthesized compounds was tested by
the DPPH free radical scavenging method. Compound I of among the tested com-
pounds exhibited the most satisfactory antioxidant activity against the DPPH radi-
cal. IC values of the thiosemicarbazones including Schiꢀ bases ranged from 19.24
5
0
to 191.06 μM.
Acknowledgements I would like to thank the Scientiꢂc Technological Research and Applications Center
(
Gübitam) and Dr. Ömer Faruk Ensari for taking the NMR spectra.
Compliance with ethical standards
Conꢁict oꢀ interest The author declares that he has no conꢁict of interest.
References
1
2
3
4
5
6
.
.
.
.
.
.
A. Goszczyńska, H. Kwiecień, K. Fijałkowski. Med. Chem. Res. 24, 3561 (2015)
A. Cinarli, D. Gürbüz, A. Tavman, A.S. Birteksöz. Bull. Chem. Soc. Ethiop. 25, 407 (2011)
A. Jarrahpour, D. Khalili, E. De Clercq, C. Salmi, J. Brunel, Molecules 12, 1720 (2007)
S. Bharti, G. Nath, R. Tilak, S. Singh, Eur. J. Med. Chem. 45, 651 (2010)
T.K. Bakır, J.B. Lawag, Res. Chem. Intermed. 46, 2541 (2020)
Y. Zhang, Y. Fang, H. Liang, H. Wang, K. Hu, X. Liu, X. Yi, Y. Peng, Bioorg. Med. Chem. Lett. 23,
1
07 (2013)
7
8
9
.
.
.
K.S. Kumar, S. Ganguly, R. Veerasamy, E. De Clercq, Eur. J. Med. Chem. 45, 5474 (2010)
S. Pandeya, D. Sriram, G. Nath, E. De Clercq, Pharm. Acta Helv. 74, 11 (1999)
M.J. Hearn, M.H. Cynamon, M.F. Chen, R. Coppins, J. Davis, H.J.-O. Kang, A. Noble, B. Tu-
Sekine, M.S. Terrot, D. Trombino, Eur. J. Med. Chem. 44, 4169 (2009)
1
1
0. S.M. Emam, I.E. El Sayed, M.I. Ayad, H.M. Hathout, J. Mol. Struct. 1146, 600 (2017)
1. B. Mohan Sahoo, S. Chandra Dinda, B.V. Ravi Kumar, J. Panda, P.S. Brahmkshatriya, Lett. Drug
Des. Discov. 11, 82 (2014)
1
1
2. S.K. Sridhar, S.N. Pandeya, J.P. Stables, A. Ramesh, Eur. J. Pharm. Sci. 16, 129 (2002)
3. M.M. Aly, Y.A. Mohamed, K.A. El-Bayouki, W.M. Basyouni, S.Y. Abbas, Eur. J. Med. Chem. 45,
3
365 (2010)
1
1
4. H. Pervez, M.S. Iqbal, M.Y. Tahir, F.H. Nasim, M.I. Choudhary, K.M. Khan, J. Enzyme Inhib. Med.
Chem. 23, 848 (2008)
5. H. Govender, C. Mocktar, H.M. Kumalo, N.A. Koorbanally, Phosphorus Sulfur Relat. Elem. 194,
1
074 (2019)
1
1
6. S. Ghosh, A.K. Misra, G. Bhatia, M. Khan, A. Khanna, Bioorg. Med. Chem. Lett. 19, 386 (2009)
7. M. Bingul, E. Şenkuytu, M.F. Saglam, M. Boga, H. Kandemir, I.F. Sengul, Res. Chem. Intermed.
4
5, 4487 (2019)
1
1
2
8. H. Muğlu, Res. Chem. Intermed. 46, 2083 (2020)
9. T.R. Bal, B. Anand, P. Yogeeswari, D. Sriram, Bioorg. Med. Chem. Lett. 15, 4451 (2005)
0. A. Kshirsagar, M.P. Toraskar, V.M. Kulkarni, S. Dhanashire, V. Kadam. Int. J. Chem. Tech. Res 1,
6
96 (2009)
2
2
1. C. Shipman Jr., S.H. Smith, J.C. Drach, D.L. Klayman, Antimicrob. Agents Chemother. 19, 682
1981)
2. N. Solak, S. Rollas, Arkivoc xii, 173 (2006)
(
1
3

Novel Schif bases derived ꢀrom isothiocyanates: synthesis,…
2
2
3. W. Hu, W. Zhou, C. Xia, X. Wen, Bioorg. Med. Chem. Lett. 16, 2213 (2006)
4. H. Pervez, N. Manzoor, M. Yaqub, A. Khan, K.M. Khan, F-u-H Nasim, M.I. Choudhary, Lett. Drug
Des. Discov. 7, 102 (2010)
2
2
5. B. Halliwell, J.M. Gutteridge, Free radicals in biology and medicine (Oxford University Press,
Oxford, 2015)
6. Y.K. Tyagi, A. Kumar, H.G. Raj, P. Vohra, G. Gupta, R. Kumari, P. Kumar, R.K. Gupta, Eur. J.
Med. Chem. 40, 413 (2005)
2
2
2
3
3
7. W. Brand-Williams, M.-E. Cuvelier, C. Berset, LWT-Food. Sci. Technol. 28, 25 (1995)
8. N. Naik, H.V. Kumar, P.B. Vidyashree, J. Pharm. Res. 4, 2686 (2011)
9. E.N. Frankel, A.S. Meyer, J. Sci. Food Agric. 80, 1925 (2000)
0. K.H.D. Reddy, S.-M. Lee, K. Seshaiah, R.K. Babu, J. Serb. Chem. Soc. 78, 229 (2013)
1. P. Tarasconi, S. Capacchi, G. Pelosi, M. Cornia, R. Albertini, A. Bonati, P.P. Dall’Aglio, P. Lunghi,
S. Pinelli, Bioorg. Med. Chem. 8, 157 (2000)
3
2. D. Williams, I. Fleming, Spectroscopic methods in organic chemistry (McGraw Hill Book Co. Ltd,
Maidenhead, 1973)
3
3
3. C. Hansch, A. Leo, R. Taft, Chem. Rev. 91, 165 (1991)
4. H. Muğlu, M.S. Çavuş, T. Bakır, H. Yakan, J. Mol. Struct. 1196, 819 (2019)
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