Synthesis, investigation of the new derivatives of dihydropyrimidines and determination of their biological activity

Article abstract of DOI:10.1016/j.molstruc.2017.03.084

We reported of synthesis and investigation of the new biologically active derivatives of dihydropyrimidines 2 and 3. The investigation of structures of compounds by various experiments of NMR spectroscopy revealed the splitting of the signals to doublets

Full text of DOI:10.1016/j.molstruc.2017.03.084

Journal of Molecular Structure 1141 (2017) 39e43
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Journal of Molecular Structure
journal homepage: http://www.elsevier.com/locate/molstruc
Synthesis, investigation of the new derivatives of dihydropyrimidines
and determination of their biological activity
,
*
A.M. Maharramov a, M.A. Ramazanov a, G.A. Guliyeva b, A.E. Huseynzada a
,
U.A. Hasanova a, N.G. Shikhaliyev a, G.M. Eyvazova a, S.F. Hajiyeva a, I.G. Mamedov a,
M.M. Aghayev a
a Baku State University, Z. Khalilov 23, Baku, AZ 1148, Azerbaijan
b Azerbaijan Republican Sanitary and Quarantine Inspection, Zargarpalan 121, Baku, AZ 1009, Azerbaijan
a r t i c l e i n f o
a b s t r a c t
Article history:
We reported of synthesis and investigation of the new biologically active derivatives of dihydropyr-
imidines 2 and 3. The investigation of structures of compounds by various experiments of NMR spec-
troscopy revealed the splitting of the signals to doublets and multiplets that confirms the presence of
diastereomers in solution of compound 2 and the presence of diastereomers and tautomers in solution of
compound 3. The individual diastereomer of compound 3 has been isolated. Biological activity of the
synthesized compounds was studied on various species of genus Aspergillus fungi.
Received 12 December 2016
Received in revised form
19 March 2017
Accepted 21 March 2017
Available online 25 March 2017
© 2017 Elsevier B.V. All rights reserved.
Keywords:
Dihydropyrimidine
Diastereomer
Tautomer
NMR spectroscopy
IR spectroscopy
Aspergillus fungi
1. Introduction
phenobarbital, thus have shown promising anti-epilepsy activity.
Dihydropyrimidines are obtained by various methods [31] and
Dihydropyrimidines, as a class of organic compounds with a
broad spectrum of biological activity, are widely used in medicine.
The biological investigations of these various molecules via mo-
lecular manipulation showed such activities as antifungal [1],
antiproliferative [1], antiviral [1], antitumor [2e7], antiin-
flammatory [8e10], antihypertensive [11e15], anti-HIV [16], anti-
epileptic [17], anti-malarial [18], antibacterial [19e22], antituber-
cular [23], miscellaneous [24e26], potassium [27e29] and calcium
channel antagonist [30]. Among the derivatives of dihydropyr-
imidines that found their application in medicine we can mention
the following drugs: batzelladine A and B [16], (S)-monastrol [2e7],
(S)-enastron [2e7], mon-97 [2e7], (R)-fluorastrol [3], terazosin [25]
and etc … Moreover, dihydropyrimidines SQ 32926, SQ 32547
which are aza-analogues of nifedipine, are promising targets for
using them as oral antihypertensive agents [1]. Dihydropyr-
imidines, studied in Ref. [17], have similar structure to
Biginelli reaction is a convenient one, due to the fact that it is a one-
pot condensation reaction, and renewed exploration of the reaction
conditions leads to obtaining of enantioenriched dihydropyr-
imidines [32]. Extraction of individual optical active compound is
very important, especially if this compound is potent to be applied
as a biologically active compound, because the presence of another
enantiomer in drug leads to severe side effects [33e35]. Moreover,
obtaining of individual enantiomer mostly is expensive in eco-
nomic terms, because of using of special conditions and catalysts.
According to above-mentioned, in some cases it is better to receive
a mixture of diastereomers, which can be easily separated.
Considering the importance of dihydropyrimidines, we carried
out Biginelli reaction and received new derivatives of dihydropyr-
imidines. Furthermore, we obtained a mixture of diastereomers
and extracted individual diastereomer. The structures of obtained
compounds were investigated by various methods, such as nuclear
magnetic resonance (NMR), Fourier transform infrared spectros-
copy (FT-IR) and elemental analysis. The biological activity of syn-
thesized compounds was also studied against various species of
genus Aspergillus fungi.
* Corresponding author.
E-mail address: alekber-92@mail.ru (A.E. Huseynzada).
http://dx.doi.org/10.1016/j.molstruc.2017.03.084
0022-2860/© 2017 Elsevier B.V. All rights reserved.

40
A.M. Maharramov et al. / Journal of Molecular Structure 1141 (2017) 39e43
2. Materials and methods
cooled with ice. The precipitate was filtered, washed with distilled
water and dried; yield is 90%, M. p. 347e350 ꢀC.
All chemicals, applied in the synthesis, were of analytical grade
and used as received. K2CO3, dimethyl sulfoxide (DMSO), 1,2-
dibromoethane, salicylaldehyde, CCl4, urea, acetylacetone, thio-
urea, ethanol, NH4Cl, acetic acid, benzaldehyde, acetone were
purchased from Sigma-Aldrich (Taufkirchem, Germany).
The control of the reactions progress and the determination of
the synthesized compounds purity were done by TLC on Sorbfil
plates, iodine vapors were used as a developer. Elemental analysis
was performed on the analyzer Carlo Erba 1108.
1H NMR spectrum of compound 2: (DMSO-d6,
d, ppm), 1.9 (6H,
2CH3), 2.3 (6H, 2CH3), 4.5 (4H, 2OCH2), 5.6 (2H, 2CH), 6.9e7.3 (12H,
2Arþ2NH), 9.1 (2H, 2NH).
13C NMR spectrum of compound 2: (DMSO-d6,
d, ppm), 19
(2CH3), 30 (2CH3), 49 (2OCH2), 67 (2CH), 108 (2C), 112 (2C), 121
(2CH, Ar), 128 (2CH, Ar), 129 (2CH, Ar), 131 (2CH, Ar), 149 (2C), 153
(2C, Ar), 157 (2CO), 195 (2CO).
Found, %: C 64.81; H 5.71; N 10.71. C28H30N4O6. Calculated, %: C
64.86; H 5.79; N 10.81.
FTIR spectrum is given in Fig. S23. The bands at 3383 cmꢁ1 and
3232 cmꢁ1 correspond to stretching vibrations of NH groups. The
intense bands at 1697 cmꢁ1 and 1598 cmꢁ1 correspond to
stretching vibrations of C]O groups. The peaks within the range
1487e1325 cmꢁ1 are corresponding to stretching vibrations of CeC
in aromatic ring. The peaks within the range 1111e1062 cmꢁ1 are
corresponding to deformation vibrations of CH groups in the plane
of aromatic ring. The band at 1234 cmꢁ1 corresponds to stretching
vibration of CAr-OCH2 group.
2.1. NMR spectra
The NMR experiments have been performed on a BRUKER FT
NMR spectrometer AVANCE 300 (Bruker, Karlsruhe, Germany)
(300 MHz for 1H and 75 MHz for 13C) with a BVT 3200 variable
temperature unit in 5 mm sample tubes using Bruker Standard
software (TopSpin 3.1). The 1H and 13C chemical shifts were refer-
enced to internal tetramethylsilane (TMS); the experimental pa-
rameters for 1H are as follows: digital resolution ¼ 0.23 Hz, SWH
(spectral width in Hz) ¼ 7530 Hz, TD (time domain) ¼ 32 K, SI
2.2.3. Synthesis of 1-[4-[2-[2-[2-(5-acetyl-1,2,3,4-tetrahydro-6-
methyl-2-thioxo-4-pyrimidinyl)phenoxy]ethoxy]phenyl]-1,2,3,4-
tetrahydro-6-methyl-2-thioxo-5-pyri-midinyl]ethanone (3)
(Fourier transform size) ¼ 16 K, 90ꢀpulse-length ¼ 10
ms, PL1 (po-
wer level for F1 channel) ¼ 3 dB, ns (number of scans) ¼ 1, ds
(number of dummy scans) ¼ 0, d1 (relaxation delay) ¼ 1 s and for
13C as follows: digital resolution ¼ 0.27 Hz, SWH ¼ 17985 Hz,
To
a solution of 2 mmol of 2.2’-(ethane-1.2-diylbis(oxy))
dibenzaldehyde in 20 ml of ethanol were added 34 mmol of thio-
urea, 17 mmol of acetylacetone and 2 mmol of NH4Cl. The reaction
mixture was heated on a water bath for 1.5 h. Subsequently, it was
cooled with ice. The precipitate was filtered, washed with distilled
water and dried; yield is 91%, M. p. 270e272 ꢀC. Extraction of in-
dividual diastereomer was implemented by dissolving in acetone,
in which it doesn't dissolve.
TD ¼ 64 K, SI ¼ 32 K, 90ꢀ pulse-length ¼ 9
ds ¼ 2, d1 ¼ 3 s.
m
s, PL1 ¼1.5 dB, ns ¼ 100,
COSY: pulse program ¼ cosygpdf, digital resolution ¼ 1.97 Hz,
SWH ¼ 2610, TD ¼ 1 K, SI ¼ 512, 90ꢀ pulse-length ¼ 10
PL1 ¼ 3 dB, ns ¼ 4, ds ¼ 16, d1 ¼ 1 s.
ms,
ROESY: pulse program ¼ roesyph, digital resolution ¼ 1.49 Hz,
SWH ¼ 3063 Hz, TD ¼ 2 K, SI ¼ 512 K, 90ꢀ pulse-length ¼ 10
PL1 ¼ 3 dB, ns ¼ 16, ds ¼ 4, d1 ¼ 2 s.
ms,
1Н NMR spectrum of compound 3: (DMSO-d6,
d, ppm), 1.9 (6H,
2CH3), 2.2 (6H, 2CH3), 4.4 (4H, 2OCH2), 5.6 (2H, 2CH), 6.9e7.3 (10H,
The NMR-grade DMSO-d6 (99.7%, containing 0.3% H2O) was
used for the solutions of 1, 2, 3, 4 and 5. TopSpin plot editor was
used to edit the 2D NMR contour plots.
2Ar), 9.3 (2H, 2NH), 10.2 (2H, 2NH), 13.4 (1H, SH).
13C NMR spectrum of compound 3: (DMSO-d6,
d, ppm), 18.3
(2CH3), 30 (2CH3), 49.8 (2OCH2), 66 (2CH), 109.3 (2C), 113 (2C), 121
(2CH, Ar), 128 (2CH, Ar), 129 (2CH, Ar), 131 (2CH, Ar), 145 (2C), 156
(2C, Ar), 174 (2CS), 195 (2CO).
2.2. IR spectra
Found, %: C 61.01; H 5.37; N 10.08; S 11.52. C28H30N4S2O4.
Calculated, %: C 61.09; H 5.45; N 10.18; S 11.63.
FTIR spectra were recorded on a Varian 3600 FTIR spectropho-
tometer in KBr tablets. The spectrum was taken in the range of
4000e400 cmꢁ1 at room temperature.
FTIR spectrum is given in Fig. S24. The bands at 3399 cmꢁ1 and
3196 cmꢁ1 correspond to stretching vibrations of NH groups. The
intense bands at 1677 cmꢁ1 correspond to stretching vibrations of
C]O group and 1187 cmꢁ1 correspond to stretching vibrations of
C]S group. The peaks within the range 1598e1285 cmꢁ1 are cor-
responding to stretching vibrations of CeC in aromatic ring. The
peaks within the range 1125e1052 cmꢁ1 are corresponding to
deformation vibrations of CH groups in the plane of aromatic ring.
2.2.1. Synthesis of 2.20-(ethane-1.2-diylbis(oxy)) dibenzaldehyde (1)
To a solution of 38.3 mmol of salicylaldehyde in 20 ml DMSO
were added 19.8 mmol of 1,2-dibromoethane and 37.7 mmol of
K2CO3. The reaction mixture was heated on a water bath for 3.5 h.
Subsequently, it was cooled with ice. The precipitate was filtered,
washed with distilled water, dried and afterwards washed with
CCl4; yield is 80%, M. p. 116e118 ꢀC.
The band at 1237 cmꢁ1 corresponds to stretching vibration of CAr
-
OCH2 group.
1H NMR spectrum of compound 1: (DMSO-d6,
2OCH2), 7e7.8 m (8H, Ar), 10.3 s (2H, COH).
d
, ppm), 4.6 s (4H,
2.2.4. Synthesis of 5-acetyl-6-methyl-4-phenyl-3.4-
dihydropyrimidin-2(1H)-one (4) and 1-(6-methyl-4-phenyl-2-
thioxo-1,2,3,4-tetrahydropyrimidin-5-il)ethanone (5) was
implemented as described in literature [36,37]
13C NMR spectrum of compound 1: (DMSO-d6,
d, ppm), 68
(2OCH2),115 (2CH, Ar),121 (2CH, Ar),125 (2C, Ar),128 (2CH, Ar),138
(2CH, Ar), 161 (2C, Ar), 190 (2COH).
Found, %: C 71.04; H 5.11. C16H14O4. Calculated, %: C 71.11; H 5.19.
1H NMR spectrum of compound 4: (DMSO-d6,
d, ppm), 2 s (3H,
CH3), 2.3 s (3H, CH3), 5.2 s (1H, CH), 7e7.5 m (5H, Ar), 7.8 s (1H, NH),
2.2.2. Synthesis of 4.40-(2.20-(ethane-1.2-diylbis(oxy)bis(2.1-
phenylene))bis(5-ace-tyl-6-methyl-3.4-dihydropyrimidin-2(1H)-
one) (2)
9.1 s (1H, NH).
13C NMR spectrum of compound 4: (DMSO-d6,
d, ppm), 19 (CH3),
30 (CH3), 55 (CH), 110 (C), 127 (2CH, Ar), 128 (CH, Ar), 129 (2CH, Ar),
145 (C), 148 (C, Ar), 153 (CO), 194 (CO).
To
a solution of 2 mmol of 2.2’-(ethane-1.2-diylbis(oxy))
dibenzaldehyde in 50 ml of ethanol were added 35 mmol of urea,
17 mmol of acetylacetone and 4 ml of ice acetic acid. The reaction
mixture was heated on a water bath for 9 h. Subsequently, it was
Found, %: C 67.74; H 6.01; N 12.1. C13H14N2O2. Calculated, %: C
67.83; H 6.09; N 12.17.
1Н NMR spectrum of compound 5: (DMSO-d6,
d, ppm), 2.1 s (3H,

A.M. Maharramov et al. / Journal of Molecular Structure 1141 (2017) 39e43
41
CH3), 2.3 s (3H, CH3), 5.3 s (1H, CH), 7.1e7.4 m (5H, Ar), 9.78 s (1H,
deficient carbon of the aldehyde function and the formation of N-
acyliminium ion intermediate [38e40]. Further, the cyclization
occurs by attack of active methylene compound on this interme-
diate in a Michael fashion [38e40].
NH), 10.3 s (1H, NH).
13C NMR spectrum of compound 5: (DMSO-d6,
d, ppm), 18.7
(CH3), 30.8 (CH3), 54.2 (CH),110.9 (C),127.2 (2CH, Ar),128.1 (CH, Ar),
129 (2CH, Ar), 143.3 (C), 145 (C, Ar), 174.5 (CS), 195.2 (CO).
Found, %: C 63.33; H 5.64; N 11.33; S 12.96. C13H14N2SO.
Calculated, %: C 63.41; H 5.69; N 11.38; S 13.
1H and 13C NMR spectra of compound 2 and 3 in DMSO-d6 so-
lution are given in Fig. S1eS4. During interpretation of 1H and 13C
NMR spectra of these compounds, we have detected the splitting of
all signals to doublets (in case of compound 2) and multiplets (in
case of compound 3).
2.3. Biological activity
Splitting of all signals to doublets and multiplets in these com-
pounds theoretically may be caused by the following reasons:
Efficiency of the investigated compounds 3, 5 and individual
diastereomer of compound 3 (IDC3) was tested on genus Aspergillus
fungi by the two traditional methods: disc-diffusion method by
using thick nutrient medium and serial dilution method in liquid
nutrient medium for the determination of the minimum inhibitory
concentration (MIC) of the tested compounds.
- The presence of keto-enol tautomerism, caused by transition of
proton from amine group to the oxygen of carbonyl group (or
presence a partial double bond between nitrogen and carbon) in
case of compound 2, and the presence of tautomerism, caused
by transition of proton from amine group to the sulphur of
thiocarbonyl group (or presence a partial double bond between
nitrogen and carbon) in case of compound 3;
According to the disc-diffusion method, 1 ml of the diurnal
suspension of the test culture (105 CFU/ml) was stratified on the
surface of thick nutrient medium (meat-peptone agar, Potato
Dextrose Agar). Inoculum was used during 15 min after prepara-
tion. Previously prepared discs with a certain concentrations were
stratified on the surface of nutrient medium by the sterile tweezers.
The weights of the samples were 0,01; 0,1; 0,2; 1; 10 and 12 mg,
respectively, and were dissolved in 1 ml of DMSO. Dishes were
incubated at 37 ꢀC during 24e48 h and in parallel at 28 ꢀC during
72e120 h. Similarly, record of the results was carried out,
comparing with control dishes without investigated compound
(solution) and with the known drug Amphotericin B. MIC of the
investigated compounds was determined by the second method e
serial dilution in liquid nutrient medium (meat-peptone broth,
Sabouraud broth). Various samples (different series) were carried
in a test-tube with a sterile broth of 4 ml volume and as a result
biological systems with various concentrations were obtained. A
day later, 0,1 ml of diurnal culture suspension was carried in them.
After exposition during 24e72 h at 28 ꢀC the inoculation of 0,1 ml of
suspension from test-tube on the surface of meat-peptone agar was
made. Record of the results was made after 24 h incubation of
dishes in thermostat at 37 ꢀC.
- Rotation around single bonds;
- The presence of diastereomers in solution (there are two
asymmetric carbon atoms in the structures of compounds 2 and
3).
In order to determine which of the reasons caused the splitting
of all signals to doublets and multiplets in the above-indicated
compounds, various NMR investigations have been carried out.
The NMR investigations of compound 2 have shown the absence
of keto-enol tautomerism (the signal from the enol hydroxyl group
hasn't been observed in 1Н NMR spectrum). Subsequently, no
changes have been observed in the splitting of the signals in the
spectra of compound 2 at the 20e95 ꢀC temperature intervals
(Figs. S5 and S6), that proves the discrepancy of first and second
reasons. Considering all facts, the splitting of the signals to doublets
in the spectra of compound 2 is caused by the presence of two
diastereomers in the solution of this compound. In order to confirm
that the reason of splitting of signals to doublet is caused by the
presence of two diastereomers in the solution of compound 2, we
synthesized known in literature compound 4 which has only one
asymmetric carbon atom (Scheme 2) and investigated its NMR
spectra.
3. Results
The fact of absence of any splitting in the spectra of compound 4
(Figs. S17 and S18) also confirms that the splitting of the signals to
doublets in the spectra of compound 2 is caused by the existing of
two diastereomers in the solution of this compound.
We obtained dialdehyde 1 by condensation of salicylaldehyde
with 1,2-dibromoethane. On the basis of this dialdehyde we carried
out a three-component Biginelli reaction and obtained new dihy-
dropyrimidines 2 and 3 (Scheme 1). The mechanism of this reaction
involved nucleophilic attack of urea (thiourea) on the electron
1H and 13C NMR spectra of compound 3 in DMSO-d6 solution are
O
O
1
O
H
H2N
NH2
+
+
+
O
O
X
Br Br
O
O
OH
H
H
O
X= O, S
O
O
O
HN
HN
X
N
X
N
H
H
X= O - (2)
X= S - (3)
Scheme 1. Reactions of synthesis of compounds 1, 2, 3.

42
A.M. Maharramov et al. / Journal of Molecular Structure 1141 (2017) 39e43
Table 4
The biological activity of Amphotericin B.
Investigated
compound
Inhibition zone of investigated
compound against A.Niger, mm
Sample
weight, mg
O
H N
2
NH
2
+
+
HN
X
O
O
Amphotericin B
12
0.01
O
X
N
H
X=O, S
H
X= O - (4)
X= S - (5)
given in Figs. S3 and S4. In comparison with the compound 2, the
signal from the enthiol group has been observed at 13.4 ppm in 1Н
NMR spectrum of compound 3. According to this data, we can
conclude that the compound 3 exists in solution in the tautomeric
form, caused by transition of proton from amine group to the
sulphur of thiocarbonyl group. It is known that in this case the
splitting of signals to doublets should be observed, but instead of
doublets, multiplets have been observed in 1H and 13C NMR spectra
of compound 3. In order to determine, which of the reasons leads to
the splitting of the signals to multiplets, NMR experiments of
compound 3 at 20, 60 and 80 ꢀС have been performed. 1H and 13C
NMR spectra of compound 3 in DMSO-d6 solution at 20, 60 and
80 ꢀС are given in Figs. S7eS12. NMR investigations of compound 3
demonstrate simplification of the signals in the spectra till dou-
blets, during increasing temperature from 20 ꢀС to 80 ꢀС, and the
complete disappearance of the signal from the enthiol group. This is
consistent with the fact that with rising of temperature the com-
plete transition of tautomer, containing enthiol group, to the most
stable tautomer, containing thiocarbonyl group, is observed. Thus,
we can conclude that the splitting of signals to multiplets in the
spectra of compound 3 is caused by the presence of tautomers and
diastereomers in solution.
In order to confirm that the reason of splitting of signals to
multiplets is caused by the presence of tautomers and di-
astereomers in solution of compound 3, we synthesized known in
literature compound 5, which has only one asymmetric carbon
atom (Scheme 2) and investigated its NMR spectra. The fact of
absence of any splitting in the spectra of compound 5 (Figs. S19 and
S20) also confirms that the splitting of signals to multiplets in the
spectra of compound 3 is caused by the presence of tautomers and
diastereomers in solution.
Scheme 2. Reactions of synthesis of compounds 4 and 5.
16 16
16 16
13
13
14
13
13
14
12
12
11
14
12
12
11
14
15
10
15 11
10
15
10
15 11
10
O
O
O
O
O
O
O
8
O
8
4
4
N
3
4
4
N
HN
HN
3
3
5
6
5
6
9
3
2
9
8
5
6
5
6
9
9
8
2
2
2
1
1
1
N
H
1
N
H
7
7
7
7
HS
N
HS
N
H
S
S
H
Scheme 3. The tautomeric transition of the compound 3.
Table 1
The biological activity of the compound 5.
Investigated compound
Inhibition zone of
investigated
compound, mm
Sample weight, mg
A. Flavus
A. Niger
Compound 5
12
15
19
25
39
45
9
0,01
0,1
0,2
1
13
19
23
29
37
10
12
Table 2
The biological activity of the compound 3.
Furthermore, individual diastereomer of compound 3 has been
isolated from the diastereomeric mixture and its individualism has
been proved by 1H and 13C NMR spectra (Figs. S13 and S14). As seen
from the 1H and 13C NMR spectra, splitting of some signals to
doublets is observed instead of multiplets, and it is related to the
tautomeric transition.
Investigated compound
Inhibition zone of
investigated
compound, mm
Sample weight, mg
A. Flavus
A. Niger
Compound 3
8
14
18
23
29
41
49
0,01
0,1
0,2
1
10
12
11
13
17
25
33
Due to the presence of two types of amine groups in the
structure of compound 3, the determination of amine group, which
takes part in the tautomeric transition, is a matter of scientific in-
terest. Comparison of 1Н NMR spectra of compound 3 at 20, 60 and
80 ꢀС allows us to conclude that the signal from amine group at
9.3 ppm participates in the tautomeric transition, due to the fact
that with the rising of temperature the constriction of this signal is
observed. In order to determine, which of the amine groups is
conformed to the signal at 9.3 ppm, 2D COSY and ROESY NMR ex-
periments have been performed (Figs. S15 and S16). As seen from
the 2D COSY and ROESY NMR spectra, the signal from the amine
group at 9.3 ppm correlates with the signal of CH group in the
position 4. Hence, we can conclude that the amine group in the
position 3 participates in the tautomeric transition, which can be
demonstrated by the following way (Scheme 3).
Table 3
The biological activity of the compound IDC3.
Investigated compound
Inhibition zone of
investigated
compound, mm
Sample weight, mg
A. Flavus
A. Niger
IDC3
9
7
0,01
0,1
0,2
1
10
12
The biological activity of compounds 3, IDC3 and 5 were
investigated against various species of genus Aspergillus fungi.
Values of inhibition concentration of compounds 3, IDC3, 5 towards
microorganisms were 0,01; 0,1; 0,2; 1; 10 and 12 mg/ml respec-
tively. It was determined that in all cases, MICs of investigated
13
16
21
29
37
8
11
14
17
19

A.M. Maharramov et al. / Journal of Molecular Structure 1141 (2017) 39e43
43
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compounds were 0,01 mg/ml. Investigated compounds showed
different activities and results are given in Table 1e3.
The highest fungal toxicity against A. Niger was revealed on
compounds 5 and 3. Record of the results was carried out,
comparing with control dishes without investigated compound
(solution) and with the known drug Amphotericin B. It was
determined that DMSO doesn't influence on various species of
genus Aspergillus fungi. The result of the Amphotericin B effect is
given in Table 4. Comparing results, we can conclude that synthe-
sized compounds demonstrate good antifungal activity against
A. Niger. Taking into consideration the structure-activity correlation
it could be supposed that pronounced antifungal activity of inves-
tigated compounds is due to the presence of NH-C(S)-NH moiety in
the molecule [41,42].
Compounds 5 and IDC3 demonstrate pronounced antifungal
properties against A. Flavus. It was found that both methods were
informative during the investigation of influence of synthesized
compounds with various concentrations on antifungal activity
against A. Niger and A. Flavus.
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084. These data include MOL files and InChiKeys of the most
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