Synthesis, antibacterial, antielastase, antiurease and antioxidant activities of new 1,4-butylene bridged bis-1,2,4-triazole derivatives

Article abstract of DOI:10.3109/14756366.2011.636359

A new bis schiffbases, 3 a-b were synthesized compound 2 with various bis aldehydes. Compounds 3 a-b have been reduced with NaBH4 to afford the corresponding bis amino triazole compounds 4 a-b. The obtained products 3 a-b and 4 a-b were identified by FTIR, H-NMR, 13C-NMR. A series of triazol derivatives were evaluated for their antibacterial, antioxidant, antiurease and antielastase activities. The results showed that the synthesized new bis-1,2,4-triazole derivatives had effective antioxidant, antiurease and antielastase activities.

Full text of DOI:10.3109/14756366.2011.636359

Journal of Enzyme Inhibition and Medicinal Chemistry, 2011, 1–6, Early Online
© 2011 Informa UK, Ltd.
ISSN 1475-6366 print/ISSN 1475-6374 online
DOI: 10.3109/14756366.2011.636359
ReseaRch aRtIcle
Synthesis, antibacterial, antielastase, antiurease and
antioxidant activities of new 1,4-butylene bridged
bis-1,2,4-triazole derivatives
Nurhan Gumrukcuoglu1, Bahar Bilgin Sokmen2, Serpil Ugras3, Halil Ibrahim Ugras2, and
Refiye Yanardag4
1Vocational School of Health Sciences, Karadeniz Technical University, Trabzon, Turkey, 2Department of Chemistry, Faculty
of Arts and Sciences, Giresun University, Giresun, Turkey, 3Department of Biology, Faculty of Arts and Sciences, Giresun
University, Giresun, Turkey, and 4Department of Chemistry Faculty of Engineering, Istanbul University, Istanbul, Turkey
abstract
A new bis schiffbases, 3 a-b were synthesized compound 2 with various bis aldehydes. Compounds 3 a-b have
been reduced with NaBH4 to afford the corresponding bis amino triazole compounds 4 a-b. The obtained products
1
3 a-b and 4 a-b were identified by FTIR, H-NMR, 13C-NMR. A series of triazol derivatives were evaluated for their
antibacterial, antioxidant, antiurease and antielastase activities. The results showed that the synthesized new bis-
1,2,4-triazole derivatives had effective antioxidant, antiurease and antielastase activities.
Keywords: Bis-aldehydes, bis-schiff bases, complexation, enzyme inhibition activity
Introduction
defense protein7. In agriculture, high urease activity
e synthesis of bis schiffbases has been attracting
increasing interest in a number of areas in chemistry as
well as biochemistry1. Schiff bases have played an impor-
tant role in the development of coordination chemistry as
they readily form stable complexes with most transition
metals2. ey are also important in diverse field’s chem-
istry has been owing to their biological activities3. ere
has been a remarkable interest in the synthesis and study
of schiff bases physical properties. Furthermore, in recent
years, some Schiff base derivatives of 1,2,4-triazoles and
their reduced derivatives have also been found to possess
pharmacological activities4.
Elastases are potent serin protease of the chymotrpsin
family that hydrolytically degrades extracellular matrix
components such as elastin, proteoglycans, fibronectin
and collagen5. Inhibition of the elastase activity could
also be used method to protect against skin aging6.
In plants, urease probably participates in systemic
nitrogen transport pathways and possibly acts a toxic
causes significant environmental and economic prob-
lems by releasing abnormally large amounts of ammo-
nia into the atmosphere during urea fertilization. Plant
damage and ammonia toxicity can be eliminated by
amending the fertilizer with a small amount of a urease
inhibitor. It is shown that these inhibitors can induce
some phytotoxicity at higher concentrations8. Urease is
directly involved in the formation of infection stones and
contributes to the pathogenesis of urolithiasis, pyelone-
phritis, hepatic encephalopathy, hepatic coma and uri-
nary catheter encrustation7. In the near past, a number
of compounds have been proposed as urease inhibi-
tors to reduce environmental problems and enhance
the uptake of urea nitrogen by plants and healthy
problems7.
Free radical oxidative processes also play a significant
pathological role in causing human disease. Many dis-
ease manifestations have been correlated with oxidative
tissue damage. Antioxidants are widely studied for their
Address for Correspondence: Halil Ibrahim Ugras, Department of Chemistry, Faculty of Arts and Sciences, Giresun University, 28049,
Giresun, Turkey. Tel: +904542161255. Fax: (+90) 4542164518. E-mail:halilugras@gmail.com
(Received 25 July 2011; revised 19 October 2011; accepted 19 October 2011)
1

2
N. Gumrukcuoglu et al.
1
capacity to protect organisms and cells from damage
induced by oxidative stress during metabolism.
In this present study, we have synthesized some new
1,2,4-bis triazole compounds and radical scavenging and
antioxidant activities for the newly synthesized com-
pounds are evaluated using four antioxidant method-
ologies. Moreover, the new synthesized compounds were
screened as urease-elastase inhibitors and antibacterial
activity.
(aromatic ring); H-NMR (DMSO-d6) δ (ppm): 1.19 (t,
12H, CH3), 1.92 (bs, 8H, CH2), 2.68–2.73 (m, 4H, OCH2),
4.16 (bs, 4H, OCH2), Ar-H: [7.09–7.12 (m, 4H), 7.83–7.88
(m, 4H)], (8.73 (s, 2H, N=CH); 13C-NMR (DMSO-d6) δ
(ppm): 166.87 (2C, N=CH), 152.11 (4C, triazole C3, C5),
Ar-C: [132.49 (4CH), 131.55 (4CH), 125.08(2C), 115.82
(2C)], 68.26 (2C, OCH2), 25.85 (2C, OCH2), 18.73 (4C,
CH2), 11.68 (4C, CH3). ESI-MS(TOF) (M+H)+:543.3313
Anal. Calc. For (C30H38N8O2):542.7082.
Synthesis of reduced compounds 4a-b
Materials and methods
e corresponding compound 3a-b (0.005 mol) was dis-
solved in dried methanol (50 mL) and NaBH4 (0.01 mol)
was added in small portions to this solution. e mixture
was refluxed for 20 min and then allowed to cool. After
evaporation at 30–35°C under reduced pressure, the
solid residue was washed with cold water. After drying
in vacuo, the solid product was recrystallized from an
appropriate solvent (1:1 ethanol-water, unless otherwise
noted) to afford the desired compound.
General
All chemicals and solvents are commercially available
and were used after distillation or treatment with drying
agents. Mp: cap. melting-point apparatus (Barnstead-
Electrothermal 9200, Iowa USA); uncorrected. IR Spectra:
solns in KBr pellets with a Perkin-Elmer 100 FTIR
spectrometer (Cambridge, England). H- and 13C- NMR
1
spectra (in DMSO): 200 (50) MHz Varian spectrometer
(Danbury, CT); δ in ppm; Me4Si as the internal standard.
Mass spectra: Agilent 6230 TOF (ESI-MS) (CA, USA).
Antioxidant activities of samples were determined in a
spectrophotometer (UV-1240, Shimadzu, Japan).
N,N’-(2,2’-(butane-1,4-diylbis(oxy))bis(2,1-phe-
nylene)bis(methylene)bis(3,5-diethyl-4H-1,2,4-triazol-
4-amine) (4a):Yield (0.39 g, 50%); m.p. 102–103°C; IR:
3239 (NH), 1600 (C=N), 1237 (C-O), 752 cm−1 (aromatic
1
ring); H-NMR (DMSOd6) δ (ppm): 1.16 (t, 12H, CH3),
Synthesis of bis-aldehydes 1a-b and amino
compound 2
1.88 (s, 8H, CH2), 4.02 (s, 4H, OCH2), 4.52 (s, 4H, OCH2),
4.78 (bs, 4H, NH-CH2), 6.45 (t, 2H, NH), Ar-H: [6.89–6.93
(m, 4H), 7.15–7.19 (m, 2H), 7.37 (d, 2H)]; 13C-NMR
(DMSO-d6) δ (ppm): 155.99 (4C, triazole C3, C5), Ar-C:
[130.84 (2CH), 130.43 (2CH), 129.25 (2CH), 128.65 (2C),
121.67 (2C), 115.83 (2CH)], 67.85 (2C, OCH2), 54.10 (2C,
NH-CH2), 26.28 (2C, OCH2), 23.70 (4C, CH2), 11.96 (4C,
CH3). ESI-MS(TOF) (M+H)+:547.3521 Anal. Calc. For
(C30H42N8O2):546.7398.
Bis-aldehydes 1a-b9 and 4-Amino-3,5-diethyl-4H-1,
2,4-triazole(2)10 were prepared by using literature
procedures.
Synthesis of bis-schiff bases 3a-b
e corresponding bis-aldehyde (0.01 mol) was added
to a solution of compound 3 (0.005 mol) in glacial acetic
acid (20 mL) and the mixture was refluxed for 16 h. After
cooling, the mixture was poured into a beaker containing
ice-water (100 mL). e precipitate formed was filtered.
After drying in vacuo, the product was recrystallized
from 1:2 benzene-petroleum ether to give the desired
compound.
N,N’-(4,4’-(butane-1,4-diylbis(oxy))bis(4,1-phe-
nylene))bis(methylene)bis(3,5-diethyl-4H-1,2,4-triazol-
4-amine) (4b): Yield (0.25 g, 49.5%); m.p. 130–131°C; IR:
3193 (NH), 1611 (C=N), 1249 (C-O), 830 cm−1 (aromatic
ring); 1H-NMR (DMSOd6) δ(ppm): 1.16 (t, 12H, CH3), 1.84
(s, 8H, CH2), 3.96 (s, 4H, OCH2), 4.00 (s, 4H, OCH2), 4.92
(bs, 4H, NH-CH2), 6.62 (bs, 2H, NH), Ar-H: [6.85–6.88 (m,
4H), 7.12–7.21 (m, 4H)]; 13C-NMR (DMSO-d6) δ (ppm):
151.46 (4C, triazole C3, C5), Ar-C: [135.87 (2C), 130.59
(2CH), 129.76 (2CH), 128.83 (2CH), 122.04 (2C), 114.21
(2CH)], 68.10 (2C, OCH2), 55.77 (2C, NH-CH2), 27.09 (2C,
OCH2), 24.13 (4C, CH2), 11.76 (4C, CH3). ESI-MS(TOF)
(M+H)+:547.3533 Anal. Calc. For (C30H42N8O2):546.7398.
Antibacterial activity was measured using the stan-
dard method of diffusion disc plates on agar11. Elastase
activity was examined by using N-succinyl-Ala-Ala-Ala-
p-nitroanilide (STANA) as a substrate and by the mea-
suring the release of p-nitroaniline at 410nm. Urease
inhibitory activity was determined according to Van Slyke
and Archilbald12. e DPPH (1,1-diphenyl-2-picrylhydra-
zyl) radical scavenging activity of the triazole derivatives
was measured according to the procedure described by
Brand-Williams13. e ABTS radical scavenging activity
of the triazole derivatives was measured according to the
(N,N’,N,N’)-N,N’-(2,2’-(butane-1,4-diylbis(oxy))
bis(2,1-phenylene)bis(methan-1-yl-1-ylidene)bis (3,5-
diethyl-4H-1,2,4-triazol-4-amine)(3a):Yield(0,93g,65%);
m.p. 100–101 °C; IR: 1600 (C=N), 1249 (C-O), 751cm−1
1
(aromatic ring); H-NMR (DMSO-d6) δ (ppm): 1.18 (t,
12H, CH3), 1.98 (bs, 8H, CH2), 2.65–2.69 (m, 4H, OCH2),
4.20 (bs, 4H, OCH2), Ar-H: [7.02–7.06 (m, 2H), 7.18–7.22
(m, 2H), 7.59–7.66 (m, 4H)], 8.89 (s, 2H, N=CH); 13C-NMR
(DMSO-d6) δ (ppm): 166.31 (2C, N=CH), 152.26 (4C,
triazole C3, C5), Ar-C: [137.05 (2CH), 135.68 (2C), 128.36
(2CH), 125.18 (2C), 121.25 (2CH), 114.20 (2CH)], 68.68
(2C, OCH2), 23.94 (2C, OCH2), 18.92 (4C, CH2), 11.84
(4C, CH3). ESI-MS(TOF) (M+H)+:543.3646 Anal. Calc. For
(C30H38N8O2):542.7082.
(N,N’,N,N’)-N,N’-(4,4’-(butane-1,4-diylbis(oxy))
bis(4,1-phenylene)bis(methan-1-yl-1-ylidene)bis (3,5-
diethyl-4H-1,2,4-triazol-4-amine) (3b): Yield (0.79, 55%);
m.p. 101–102°C IR: 1605 (C=N), 1251 (C-O), 831 cm−1
GENZ 636359
Journal of Enzyme Inhibition and Medicinal Chemistry

1,4-Butylene bridged bis-1,2,4-triazole derivatives
3
procedure described by Arnao, Cano and Acosta14. e
reducing power of the of the triazole derivatives was mea-
sured according to the method of Oyaizu15. For the reduc-
ing ability of triazole derivatives, the cupric ions reducing
power capacity was also used16 with slight modifications.
convenient method using NaBH4 as a selective reducing
agent was employed for the synthesis in good yields of
the corresponding bis amino triazole compounds 4a-b
(Scheme 2).
In the IR spectra of compounds 3a-b the character-
istic C=N absorption bands appeared at around 1600–
1605 cm−1. e 1H-NMR signals for the -N=CH group were
observed between δ 8.73–8.89 ppm. e 13C-NMR signals
for the−N=CH- group were recorded at δ 161–163 ppm.
Reduced compounds 4a-b showed IR absorption bands
Results and discussion
In this study, a convenient method was established for
the synthesis in good yields of new bis triazole schiff
bases 3a-b and corresponding bis amino triazole com-
pounds 4a-b. Four new bis-(4H-1,2,4-triazole) deriva-
tives synthesized in the study are exhibit some biological
activities and these results are reported.
e syntheses of bis triazole schiff bases 3a-b were
accomplished according to the reactions shown in
schemes. First, bis-aldehydes 1 were synthesized using
a published method9, as indicated in schemes. 3,5-di-
ethyl-4-amino-4H-1,2,4-triazole 2 was prepared by using
literature procedures10. Finally reactions of compounds
1 and 2 afforded the desired compounds 3a-b (Scheme
1). In general, reduction of imine type compounds is
possible, but attempts to reduce imines such as 3a-b may
also lead to a reduction of the heterocyclic ring. For this
reason, the selective reduction of the imino group pres-
ent in compounds 3a-b without affecting the heterocyclic
ring was another aim of the study. us, a general and
1
around 3194–3239 cm−1 (υNH). e H-NMR signals for
the -NH-CH2- group of these compounds were observed
as a doublet at around δ 3.96–4.02 ppm and the proton
signals of−NH-CH2- groups were recorded as a triplet or
strong singlet between δ 6.45–6.62 ppm. In the 13C-NMR
the triazole C3 and C5 of the bis-schiff base derivatives
3a-b were observed between δ 152.11–152.26 ppm and
the triazole C3 and C5 signals of the reduced compounds
4a-b were observed between δ 155.46–155.99 ppm.
Antibacterial activity was measured using the standard
method of diffusion disc plates on agar, but unfortunately,
a few ligands compounds do show biological activity
against the studied microorganisms. Antibacterial activ-
ity results were given in Table (in supp. File).
e inhibition effect of elastase activity is shown in
Table 1. We have found that all concentrations exerted
inhibitory effects on elastase in a dose-dependent
Scheme 1
Scheme 2
© 2011 Informa UK, Ltd.
GENZ 636359

4
N. Gumrukcuoglu et al.
Table 1. e elastase and urease inhibitory activity of different concentrations of triazole derivatives.
Compounds
3a
Triazole derivatives concentration (µg/mL)
Elastase IC50 (µM)*
Urease IC50 (µM)*
0.001
0.01
0.1
2.56 0.028
2.44 0.049
1
3b
0.001
0.01
0.1
0.00207 1.14 10−5
2.52 0.070
0.00212 4.241 10−5
3.31 0.141
-
2.62 0.049
2.57 0.049
2.51 0.042
1
4a
0.001
0.01
0.1
1
4b
0.001
0.01
0.1
1
Ursolic acid
Hydroxy urea
*Mean SD.
0.001
0.01
0.1
-
1
0.001
0.01
0.1
14.29 0.06
1
manner. e inhibition was increased with increasing
triazole concentration (Table 1). Compound 3b proved
to be the most potent showing an enzyme inhibitory
activity with an IC50 = 0.00207 µM. All of the compounds
showed high potent activity (IC50= 0.00207, 0.00212,
2.52, 2.56 µM) than that of standard ursolic acid
(IC50 = 3.31 0.141 µM).
Almost all compounds showed moderate to good
urease inhibitory activity (Table 1). e inhibition
was increased with increasing triazole concentration.
IC50 values for triazole compounds were found to be
2.44, 2.51, 2.57 and 2.62 µM. Compound 3a proved
to be the most potent showing an enzyme inhibition
activity with an IC50 = 2.44 0.049 µM. e least active
compound 3b had an IC50 = 2.62 0.049 µM. All of the
compounds showed high potent activity (IC50= 2.44,
2.51, 2.57, and 2.62 µM) than that of standard hydroxy
urea (IC50 = 14.29 0.06 µM).
Triazoles have been regarded as structural type
inhibitors of urease. 1,2,3 - Triazole and 1,3,4-thia-
diazole derivatives were synthesized by Khan et al.17.
ese synthesized compounds showed potent urease
inhibitor activity between IC50 = 45.60 - 459.56 µM.
is compounds had a lower urease inhibitor activity
than our triazole compounds (IC50 = 2.44–2.62 µM). In
the other study18, all synthesized triazol compounds
(IC50 = 22–43.8 µM) had a lower urease inhibitor activ-
ity than our study. e triazole derivatives may be
regarded as substrate like inhibitors on the basis of
their structural similarity with the natural substrate of
urease i.e. urea. Since all the synthesized triazole com-
pound promising urease inhibitor activity, this may be
due to their basic skeleton.
In the present study, the antioxidant activities of the
synthesized compounds (3a, 3b, 4a, 4b) were determined
in vitro with different bioanalytical methodologies.
Antioxidant capacity is widely used as a parameter for
medicinal bioactive components. e antioxidant activ-
ity of the compounds was compared with BHT. ese
comparisons were performed using a series of in vitro
tests including DPPH, ABTS radical scavenging activities
and reducing power by two methods (Fe3+- Fe2+ transfor-
mation and cuprac assays).
DPPH is used as a free radical to evaluate the anti-
oxidative activity of some natural and synthetic sources.
e scavenging of the stable DPPH radical model is a
widely used method to evaluate antioxidant activities
in a relatively short time compared with other methods.
e inhibitory effects of different concentrations of syn-
thesized compounds on DPPH radical are presented in
Table 2. eir comparable scavenging activities were also
expressed in IC50 (the effective concentration at which the
DPPHradicalswerescavengedby50%)value(Table2). All
the tested compounds showed lower free radical scaveng-
ing activities when compared BHT (IC50 = 1.43 0.01 mM).
Compound 3a showed potent DPPH free radical activity
(IC50 = 5.72 0.32 mM). Compounds 4a exhibited moder-
ateeffectonDPPHradicalwith(IC50 = 7.30 0.50 mM).e
least active compound 3b had an IC50 = 16.41 0.19 mM. It
has been reported that 1,2,4 triazole derivatives showed a
GENZ 636359
Journal of Enzyme Inhibition and Medicinal Chemistry

1,4-Butylene bridged bis-1,2,4-triazole derivatives
5
Table 2. DPPH and ABTS radical scavenging activity of different concentrations of triazole derivatives.
Triazole derivatives
Triazole derivatives
Compounds
3a
concentration (µg/mL)
DPPH IC50 (mM)*
concentration (µg/mL)
ABTS IC50 (mM)*
500
1000
1500
2000
500
250
500
750
1000
250
500
750
1000
250
500
750
1000
250
500
750
1000
250
500
750
1000
5.72 0.32
6.91 0.24
3b
8.80 0.14
1000
1500
2000
500
16.41 0.19
7.30 0.50
14.72 0.55
1.43 0.01
4a
1000
1500
2000
500
9.01 0.21
7.36 0.28
1.30 0.09
4b
1000
1500
2000
500
BHT
1000
1500
2000
*Mean SD
Table 3. Reducing power and Cupric ions reducing antioxidant capacity of different concentrations of triazole derivatives.
Triazole derivatives
Reducing power
Triazole derivatives
Compounds
3a
concentration (µg/mL)
absorbance*
concentration (µg/mL)
Cuprac method absorbance*
0.227 0.002
0.230 0.0028
0.248 0.002
0.255 0.004
0.220 0.011
0.221 0.009
0.232 0.004
0.233 0.004
0.225 0.002
0.246 0.004
0.265 0.006
0.291 0.005
0.221 0.004
0.223 0.002
0.224 0.002
0.237 0.003
0.595 0.013
0.947 0.069
1.331 0.088
1.490 0.100
250
500
0.112 0.002
0.124 0.002
0.132 0.001
0.143 0.002
0.112 0.014
0.107 0.001
0.117 0.003
0.123 0.001
0.105 0.002
0.110 0.002
0.116 0.002
0.125 0.001
0.099 0.002
0.104 0.001
0.114 0.003
0.121 0.003
0.301 0.018
0.432 0.027
0.655 0.043
0.786 0.038
25
50
750
75
1000
250
100
25
3b
500
50
750
75
1000
250
100
25
4a
500
50
750
75
1000
250
100
25
4b
500
50
750
75
1000
250
100
25
BHT
500
50
750
75
1000
100
*Mean SD.
high DPPH radical scavenging effect (IC50 = 242.49–292.38
µM)17. It was evident that 1,2,4 triazole derivatives had
a stronger effect on the DPPH radical compared to our
compounds (IC50 = 5.72–16.41 mM).
ABTS radical can directly react with antioxidants.
DPPH and ABTS radical scavenging assays have been
used to evaluate the antioxidant activity of compounds
due to the simple, rapid, and reproducible procedures of
compounds. Table 2 shows the ABTS radical scavenging
activity of triazole derivatives and standard. Lower IC50
values indicate higher ABTS radical scavenging ability. All
of the compounds (6.91–9.01 mM) showed lower ABTS
radical scavenging activity than BHT (1.30 0.09 mM).
ABTS radical scavenging activity of triazole compounds
and standard compounds exhibited the following order:
BHT 〉 3a 〉 4b 〉 3b 〉 4a (Table 2).
© 2011 Informa UK, Ltd.
GENZ 636359

6
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e reducing powers of the compounds were observed
at different concentrations, and results were compared with
BHT (Table 3). e reducing capacity of a compound may
serve as a significant indicator for its potential antioxidant
activity19. In this study, the reducing ability of compounds
synthesized augmented with increasing concentration
of samples. Compounds 3a, 3b, 4a, 4b were given similar
results.ehigheractivitywasfoundatcompound4a.Tested
compounds showed lower activity than BHT at 1000 µg/mL
concentration. ere was a correlation found between the
reducing capabilities and substituents. Reducing power of
triazole compounds and standard compounds exhibited
the following order: BHT〉 3a 〉 4a 〉 3b 〉 4b (Table 3).
e reducing power associated with antioxidant
activity reflects the electron donating capacity of bioac-
tive compounds. Antioxidants can be reductants and
inactivators of oxidants. e cupric ion (Cu2+) reducing
ability (Cuprac method) of triazole derivatives is shown
in Table 3. e cupric ion (Cu2+) reducing capability of
triazole derivatives by the cuprac method was found to
be concentration dependent (25–100 μg/mL). e cupric
ion reducing power of triazole derivatives and BHT is as
follows at the same concentration (100 μg/mL): BHT 〉
4a 〉 3a 〉 4b 〉 3b (Table 3).
Inthisstudy,theresultsshowedthatthesynthesizednew
bis-1,2,4- triazole derivatives had antioxidant, antibacte-
rial, antiurease and antielastase activities. For reason, new
bis-1,2,4- triazole derivatives may be considered as a main
elastase and urease inhibitory and free radical scavenger.
erefore, these compounds could be used as a source of
antioxidant, antielastase, antibacterial and antiurease in
pharmaceutical, cosmetic and agriculture industries.
15. Oyaizu M. Studies on products of browning reactions: Antioxidative
activities of products of browning reaction prepared from
glucosamine. Japan J Nutr 1986;44:307–315.
16. Güngör N, Ozyürek M, Güçlü K, Cekiç SD, Apak R. Comparative
acknowledgments
evaluation
of
antioxidant
capacities
of
thiol-based
antioxidants measured by different in vitro methods. Talanta
2011;83:1650–1658.
17. Khan I, Ali S, Hameed S, Rama NH, Hussain MT, Wadood A et al.
Synthesis, antioxidant activities and urease inhibition of some new
1,2,4-triazole and 1,3,4-thiadiazole derivatives. Eur J Med Chem
2010;45:5200–5207.
e author thanks to the Zihni DEMIRBAG for his
contribution.
Declaration of interest
18. Akhtar T, Hameed S, Khan KM, Choudhary MI. Syntheses,
urease inhibition, and antimicrobial studies of some chiral
e authors report no conflicts of interest.
3-substituted-4-amino-5-thioxo-1H,4H-1,2,4-triazoles.
Chem 2008;4:539–543.
19. Meir S, Kanner J, Akiri B, Hadas SP. Determinating and
involvement of aqueus reducing compounds in oxidative
defense systems of various senescing leaves. J Agric Food Chem
1995;43:1813–1819.
Med
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GENZ 636359
Journal of Enzyme Inhibition and Medicinal Chemistry