Synthesis, characterization and investigation of antibacterial and antifungal activities of novel 1,3-butadiene compounds

Article abstract of DOI:10.1080/00397911.2020.1799010

The nitro group–substituted perhalogenobuta-1,3-diene (1) is important synthetic precursor in the synthesis of different heterocycles groups with high biological activity. Firstly, new N,S-substituted-perhalonitro-1,3-butadiene compounds were synthesized

Full text of DOI:10.1080/00397911.2020.1799010

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/lsyc20
Synthesis, characterization and investigation of
antibacterial and antifungal activities of novel 1,3-
butadiene compounds
Serdar Goksin Aydinli , Yasemin Ozdamar , Cigdem Sayil , Nahide
Gulsah Deniz , Maryna Stasevych , Viktor Zvarych , Olena Komarovska-
Porokhnyavets & Volodymyr Novikov
To cite this article: Serdar Goksin Aydinli , Yasemin Ozdamar , Cigdem Sayil , Nahide
Gulsah Deniz , Maryna Stasevych , Viktor Zvarych , Olena Komarovska-Porokhnyavets &
Volodymyr Novikov (2020): Synthesis, characterization and investigation of antibacterial and
antifungal activities of novel 1,3-butadiene compounds, Synthetic Communications, DOI:
10.1080/00397911.2020.1799010
To link to this article: https://doi.org/10.1080/00397911.2020.1799010
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https://doi.org/10.1080/00397911.2020.1799010
Synthesis, characterization and investigation of
antibacterial and antifungal activities of novel
1,3-butadiene compounds
Serdar Goksin Aydinlia , Yasemin Ozdamara, Cigdem Sayila
,
Nahide Gulsah Deniza , Maryna Stasevychb , Viktor Zvarychb
Olena Komarovska-Porokhnyavetsb , and Volodymyr Novikovb
,
aEngineering Faculty, Department of Chemistry, Division of Organic Chemistry, Istanbul University-
b
Cerrahpasa, Istanbul, Turkey; Department of Technology of Biologically Active Substances, Pharmacy
and Biotechnology, Lviv Polytechnic National University, Lviv, Ukraine
ABSTRACT
ARTICLE HISTORY
Received 27 April 2020
The nitro group–substituted perhalogenobuta-1,3-diene (1) is import-
ant synthetic precursor in the synthesis of different heterocycles
groups with high biological activity. Firstly, new N,S-substituted-per-
halonitro-1,3-butadiene compounds were synthesized by the reac-
tions of various amino or thiol containing nucleophiles with 1. The
structures of all new compounds have been identified by using spec-
KEYWORDS
Antifungal activity;
antibacterial activity;
heterocyclic ring–substi-
tuted 1,3-butadiene;
piperazine; thiol
1
troscopic techniques (FT-IR, H-NMR, 13C-NMR, MS and microanalysis).
Secondly, their antimicrobial properties were tested as potential anti-
bacterial and antifungal agents. Antimicrobial activity of synthesized
N,S-substituted perhalonitrobutadienes 4a–j and 5a–d was evaluated
against Escherichia coli B-906, Staphylococcus aureus 209-P, and
Mycobacterium luteum B-917 bacteria and Candida tenuis VKM Y-70
and Aspergillus niger F-1119 fungi and the compounds 4c, 4d, 5a and
5b with high antifungal action against test-culture Aspergillus niger at
MIC values 0.9–1.9 lg/cm3 were identified as the most potent.
GRAPHICAL ABSTRACT
CONTACT Nahide Gulsah Deniz
yurdakul@istanbul.edu.tr
Supplemental data for this article can be accessed on the publisher’s website.
ß 2020 Taylor & Francis Group, LLC

2
S. G. AYDINLI ET AL.
Introduction
The chemistry of nitro group–substituted perhalogeno-1,3-butadienes has been widely
studied over the years. Particular interest in this class of compounds mainly arises from
their modifiability potential as multi directional starting materials in the synthesis of
various heterocycles groups with high biological activity. An additional nitro substituent
to perhalobutadienes to provide the corresponding perhalonitrobutadienes effecting the
biological activity and also addition of halogens to conjugated systems should increase
the chemical stability of these compounds due to the steric and electronic properties of
the halogen atom. So, perhalogeno-1,3-butadienes turn into powerful electrophiles that
react well with nucleophiles. The conjugated systems of butadiene unit are often struc-
tural components of most bioactive active compounds, including intermediates and nat-
ural products, as well as pharmaceuticals. Most perhalonitro-1,3-butadiene derivatives
show biological activity as a drug or plant protective agent.[1–6]
The six-membered saturated moiety containing nitrogen atoms as some morpholine,
thiomorpholine and piperazine analogs have been reported as a great interest for their
biological activities in a number of different therapeutic areas such as anticancer, anti-
fungal, antibacterial and antimalarial.[7–8] These heterocyclic amine derivatives owing to
important activity properties are also used in psychological and neurological researching
fields to obtain the new molecules with more better biological effect as to treat disorders
like psychosis, schizophrenia, depression and anxiety.[9–10]
Perhalonitro-1,3-butadienes readily reacts with various thiols or secondary aliphatic
amines, such as morpholine, thiomorpholine and piperazine. Thus, N,S-substituted per-
halonitro-1,3-butadiene derivatives can be obtained by the click synthesis of polyhaloni-
tro-1,3-butadiene with nucleophilies in nucleophilic vinylic substitution reaction. So, the
synthesis of hetero group substituted 1,3-butadine compounds starts with nucleophile
attack as thiols or amines to perhalonitrobutadiene molecules. Some of the S-, S,S- and
N,S-substituted perhalonitrobutadiene derivatives have been synthesized in the litera-
ture before.[11–28]
Firstly, the aim of this study was the synthesis of new N,S-substituted-nitro-1,3-buta-
diene compounds and characterization of their structures by using the various
spectroscopic techniques. We inspired by the biological importance of mono-(S)-substi-
tuted-nitro-1,3-butadiene compounds and nucleophilies such as piperazine,
aniline, thiol, etc. Secondly, we know that there were very few related literature on
investigation of biological properties of 1,3-butadiene compounds that allowed us to
synthesize new N, S-substituted butadiene compounds. It should be noted, that only
two works about biological properties of N,S-substituted-1,3-butadiene compounds,
which belong to our group, was published.[14,19] Therefore, the aim of our study was
the synthesis and characterization of novel N,S-substituted perhalo-nitro-1,3-butadiene
compounds and their study as perspective antibacterial and antifungal agents.
Results and discussion
Chemistry
The SNvin reactions of the nitro-substituted perhalobuta-1,3-diene (1) with one molar
equivalent of thiols such as 1-octanethiol or 4-methoxythiophenol without any solvent gave

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3
mono(thio)substituted perhalonitrobutadienes (2 and 3) at room temperature. The nitro-
substituted perhalobuta-1,3-diene which are interesting with their electronic structure can
be used for different synthetic applications because the reactions can be carried out by vari-
ous methods with nucleophilic vinylic substitution (SNVin) via additional-elimination routes.
The proposed mechanism for the synthesis of mono-S-substituted nitrodienes was given on
the Scheme 1. These substitution reaction continues with the addition-elimination reaction
mechanism (Scheme 1). First, the reagent attacking the C, C double bond is added, and in a
second step the intermediate is stabilized by removing hydrogen chloride.
2-Nitro-1,3,4,4-tetrachloro-1-octylthio-1,3-butadiene (2)[27] and 2-nitro-1,3,4,4-tetra-
chloro-1-(4-methoxyphenylthio)-1,3-butadiene (3)[28] reacted with the piperazine deriva-
tives to give the new compounds 4a–j and with amine derivatives to give the new
compounds 5a–d (Scheme 2). We know that mono- and N,S-substituted nitrobutadiene
compounds yielded as a single E-isomer instead of mixture of E/Z isomer according to
our previously related literature.[18–21,29–37] The exact structures of our mono- and N,S-
substituted nitro butadiene compounds were investigated by all spectroscopic data and
also especially X-ray single-crystal diffraction method in our previously literature.[34–36]
In the crystal structures of mono(thio)- and N, S-substituted nitrodienes reported in
Scheme 1. The proposed mechanism for the synthesis of S-substituted nitrodienes [18].
Cl
SR
Cl
HNR1R2
NR1R2
Cl
NO2
4a-j
Cl
Cl
Cl
Cl
RSH
Cl
Cl
Cl
SR
Cl
NO2
Cl
NO2
Cl
SR
H2N - Ar
1
Cl
2, R = CH3-(CH2)6CH2-
3, R = p-H3CO-C6H4-
NH-Ar
Cl
NO2
5a-d
4a: R = CH3-(CH2)6CH2-, R1R2 = furan-3-carbonyl piperazino
4b: R = CH3-(CH2)6CH2-, R1R2 = 3,4-dichlorophenyl piperazino
4c: R = CH3-(CH2)6CH2-, R1R2 = bis(4-fluorophenyl)methyl piperazino
4d: R = CH3-(CH2)6CH2-, R1R2 = 4-fluorobenzyl piperazino
4e: R = CH3-(CH2)6CH2-, R1R2 = 2-pyridyl piperazino
5a: R = CH3-(CH2)6-CH2-, Ar = 4-morpholino anilino
5b: R = CH3-(CH2)6-CH2-, Ar = 2-naphthyl amino
5c: R = p-H3CO-C6H4-, Ar = 4-morpholino anilino
5d: R = p-H3CO-C6H4-, Ar = 2-naphthyl amino
4f: R = p-H3CO-C6H4-, R1R2 = furan-3-carbonyl piperazino
4g: R = p-H3CO-C6H4-, R1R2 = 3,4-dichlorophenyl piperazino
4h: R = p-H3CO-C6H4-, R1R2 = bis(4-fluorophenyl)methyl piperazino
4i: R = p-H3CO-C6H4-, R1R2 = 4-fluorobenzyl piperazino
4j: R = p-H3CO-C6H4-, R1R2 = 2-pyridyl piperazino
Scheme 2. Synthesis of S- and N,S-substituted-2-nitro-1,3-butadienes (4a–j and 5a–d).

4
S. G. AYDINLI ET AL.
our previous studies, it was proved that mono(thio)substituted nitrobutadienes were E-
isomers and N, S-substituted nitrobutadienes were also E-isomers.[18–21,24,29–36] As a
consequence, it might be thought that the derived new nitrodiene products were prob-
ably E-isomers.
In the IR spectra of synthesized compounds 4a–j and 5a–d symmetrical vibrations of
nitro groups appear as strong bands in the region 1235–1294 cmꢀ1, to asymmetrical
vibrations correspond the bands within 1504–1548 cmꢀ1. The IR spectra showed a
characteristic >C¼O band at 1713 cmꢀ1 for 4a and at 1749 cmꢀ1 for 4f. In compounds
5a–d, the (N-H) stretching bands occur at 3165 cmꢀ1, 3172 cmꢀ1, 3150 cmꢀ1 and
3177 cmꢀ1, respectively.
1
In the H NMR spectra of compounds synthesized 4a–j and 5a–d, aromatic protons
usually show up in the range of d ¼ 6.30–8.30ppm and compounds 4a, 4b, 4c, 4d, 4h
and 4i which contain the piperazine ring, the piperazine ring protons were observed as
two broad singlet in the regions at d ¼ 2.12–3.73 and d ¼ 3.52–3.98ppm, respectively. In
compound 4e, piperazine protons were observed as one broad singlet in the region at
d ¼ 3.74ppm. In compounds 4f and 4j, piperazine protons appear as multiplet in two
regions at d ¼ 3.46–3.58 and at d ¼ 3.00–3.75ppm, respectively. In compound 4g, pipera-
zine protons were observed as one broad singlet and multiplet in two regions at
d ¼ 2.91ppm and d ¼ 3.55–3.70ppm, respectively. In compounds 5a and 5c which con-
tain the morpholine ring showed the morpholine ring protons (N-CH2 and O–CH2) as
two signals as tertiary at d ¼ 3.22, 3.89 and at d ¼ 3.13, 3.87ppm, respectively.
Compounds 5a-d gave a characteristic singlet bands at d ¼ 12.04, 12.16, 11.72 and
11.84ppm for the protons of the (–NH) group, respectively.
In the 13C NMR spectra of compounds 4a–j signals were observed at
d ¼ 44.11–53.41 ppm for the methylene carbon atoms of the piperazine ring and also for
the compounds 5a and 5j, signals were observed at d ¼ 48.65–68.13ppm for the methy-
lene carbon atoms of the morpholine ring. For the compounds 4a and 4f, due to the aro-
matic ring of furoyl, signals for were observed at d ¼ 147.22 and d ¼ 147.24ppm for the
furoyl (C–O) carbons and d ¼ 158.97 and d ¼ 166.06ppm for carbonyl (>C¼O) carbons,
respectively.
The MS[þESI] mass spectrum of the compounds 4b and 4g, the respective molecular
ion peaks was observed at m/z (%) 575.9 (100) [M]þ and m/z (%) 569.8 (100) [M]þ,
respectively. The compounds 4a, 4c, 4d, 4f and 4h revealed at m/z (%) 547.9 (100)
[Mþ 23]þ, m/z (%) 655.9 (100) [M þ 23]þ, m/z (%) 561.9 (100) [M þ 23]þ, m/z (%)
541.9 (100) [Mþ 23]þ and m/z (%) 649.8 (100) [Mþ 23]þ, respectively which corre-
sponds to the addition of one sodium ion. The results of MS[þESI] mass spectrum of all
the remaining compounds agree well with corresponding fragments in simi-
lar compounds.
Antibacterial and antifungal activities
New synthesized N,S-substituted-polyhalo-2-nitro-1,3-butadiene compounds 4a–j and
5a–d were evaluated for their antibacterial and antifungal activity against test cultures
of Escherichia coli B-906, Staphylococcus aureus 209-P, and Mycobacterium luteum B-

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5
917 bacteria and Candida tenuis VKM Y-70 and Aspergillus niger F-1119 fungi using
diffusion method[38] and serial dilution method[39] to search new perspective antimicro-
bial agents. Results of the biological study were presented in Tables 1 and 2. Biological
activities of heteroatom-substituted 1,3-butadiene compounds 4a–j and 5a–d were com-
pared with the known antibacterial agent vancomycin and antifungal agent nystatin (as
control C).
The S. aureus bacteria strain was sensitive to compound 5b at a concentrations of
0.5% and 0.1% and the diameter of the inhibition zone was 15.0 and 13.0 mm, respect-
ively. Compounds 4a–j and 5a–d (at 0.1% concentration) have no antibacterial and
antifungal activity against E. coli, M. luteum bacteria and C. tenuis fungus (using diffu-
sion method, Table 1). Compounds 5b and 5d have moderate activity against test cul-
ture M. luteum (10.0 mm at a concentration of 0.5%). For compounds 4a–j and 5a–d,
antifungal activity against A. niger was observed between 7.0 and 10.0 mm at concentra-
tions of 0.5% and 0.1%. The S. aureus bacteria strain was sensitive to compound 5d at a
concentration of 0.5% and the diameter of the inhibition zone was 13.0 mm (Table 1).
The biological activity results of the synthesized compounds (4a–j and 5a–d) using
serial dilution method were classified as follows: the antibacterial/antifungal activity was
considered as significant, when the minimum inhibition concentration (MIC) was
Table 1. Antimicrobial activity of the synthesized compounds determined by diffusion method.
Inhibition diameter of microorganism growth, mm
Bactericidal activity
Fungicidal activity
C. tenuis A. niger
Compound
Concentration/%
E. coli
S. aureus
M. luteum
4a
0.5
0.1
0.5
0.1
0.5
0.1
0.5
0.1
0.5
0.1
0.5
0.1
0.5
0.1
0.5
0.1
0.5
0.1
0.5
0.1
0.5
0.1
0.5
0.1
0.5
0.1
0.5
0.1
0.5
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
14.0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
10.0
0
0
0
10.0
0
18.0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
19.0
7.0
0
10.0
4b
4c
4d
4e
4f
0
10.0
7.0
10.0
7.0
10.0
8.0
7.0
0
10.0
0
7.0
0
7.0
0
10.0
0
7.0
0
10.0
7.0
10.0
8.0
10.0
7.0
20.0
4g
4h
4i
0
0
0
0
4j
5a
5b
5c
5d
0
15.0
13.0
0
0
13.0
0
15.0
ꢁ
C
ꢁ
Vancomycin was used as a control in the tests of antibacterial activity of the synthesized compounds and Nystatin
was used in the tests of antifungal action.

6
S. G. AYDINLI ET AL.
Table 2. Bactericidal and fungicidal activity of the synthesized compounds determined by serial dilu-
tion method (only compounds with positive results are included in the table).
Minimal inhibition concentration MIC, mg/cm3
Compound
E. coli
S. aureus
M. luteum
C. tenuis
A. niger
4c
4d
5a
5b
5d
þ
þ
þ
þ
þ
þ
þ
þ
0.9
0.9
1.9
0.9
þ
þ
þ
þ
þ
þ
62.5
500.0
3.9
125.0
500.0
7.8
þ
þ
þ
ꢁ
C
31.2
7.8
15.6
ꢁ
Vancomycin was used as a control in the tests of antibacterial activity of the synthesized compounds and Nystatin
was used in the tests of antifungal action.
“þ” - Growth of microorganisms
100 lg/cm3 or less; moderate, when the MIC was 100.0–500.0 lg/cm3; weak, when the
MIC was 500.0–1.000 lg/cm3; and inactive when the MIC was above 1.000 lg/cm3.
Vancomycin and nystatin were used as controls. Evaluation of antibacterial activity of
synthesized compounds 5b and 5d showed that 5b and 5d have MIC ¼ 62.5 and
500.0 mg/cm3, for S. aureus and also have MIC ¼ 125.0 mg/cm3 and 500.0 mg/cm3 for
strain of M. luteum bacteria (using serial dilution method, Table 2). Compounds 4c, 4d,
5a, 5b and 5d have no antimicrobial activity against Gram-negative bacteria E. Coli.
The only compounds 4c, 4d, 5a, 5b and 5d with positive results are included in the
Table 2.
Investigation of the antifungal activity of the synthesized compounds showed that 4c,
4d, 5b and 5a were the most potent for fungus A.niger with MIC ¼ 0.9 lg/cm3 and
1.9 lg/cm3, respectively. Compounds 4c, 4d, 5a and 5b (Fig. 1) had more lower MIC
values against test culture of A.niger, when nystatin (control) has MIC ¼ 15.6 mg/cm3
(Fig. 2). It was determined, that these compounds have no antifungal activity against C.
tenuis fungus.
Therefore, octylthio and piperazine ring substituted polyhalo-nitro-1,3-butadiene
derivatives 4c, 4d, 5a and 5b have synthesized that are the good promising candidates
with respect to biological activity as potential antifungal agents against A. niger
(Figs. 1, 2).
Materials and methods
Apparatus
Melting points were measured on a Buchi B-540 melting point apparatus. TLC plates
silica 60 F254 (Merck, Darmstadt), detection with ultraviolet light (254 nm). Elemental
analyses were performed on a Thermo Finnigan Flash EA 1112 Elemental analyzer.
Infrared (IR) spectra were recorded in ATR method on a Perkin Elmer Precisely
1
Spectrum One FTIR spectrometry. H and 13C NMR spectra were recorded on Varian
UNITYINOVA operating at 500 MHz. Mass spectra were obtained on a Thermo
Finnigan LCQ Advantage MAX LC/MS/MS spectrometer according to ESI probe.
Products were isolated by column chromatography on Silica gel (Fluka Silica gel 60,
particle size 63–200 mm). All chemicals were reagent grade and used without further
purification. Moisture was excluded from the glass apparatus using CaCl2 drying tubes.

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Figure 1. Structures of 4c, 4d, 5a and 5 b as potential antifungal agents against test-culture A. niger.
Figure 2. Minimal inhibition concentrations (mg/cm3) of 4c, 4d, 5a, 5 b and Nystatin against test-
culture A. niger.
Solvents, unless otherwise specified, were of reagent grade and distilled once prior
to use.
Synthesis
Preparation of compounds (4a–j and 5a–d)
As starting materials, 2-nitro-1,3,4,4-tetrachloro-1-octylthio-1,3-butadiene (2) and 2-
nitro-1,3,4,4-tetrachloro-1-(4-methoxyphenylthio)-1,3-butadiene (3) were prepared from
reactions of pentachloro-2-nitro-1,3-butadiene (1) with alkylthiols.[26–28] To a solution

8
S. G. AYDINLI ET AL.
Table 3. Parameters of results evaluation by the method of compound diffusion
in agar.
Zone diameter of microorganisms growth inhibition, mm
Degree of microorganism sensitivity
11ꢀ15
16ꢀ25
>25
Low sensitive
Sensitive
Highly sensitive
of 2 or 3 in 10 mL of dichloromethane as a solvent was added in equimolar amount
with vigorous stirring the respective aromatic and heterocyclic amine derivatives in
10 mL of dichloromethane at room temperature until completion of the reaction. The
mixture was stirred for 4 h and the crude products were extracted with chloroform
(3 ꢂ 50 mL). The combined organic phases were washed with water (2 ꢂ 30 mL) and
dried over anhydrous calcium chloride or magnesium sulfate in vacuo. The products
were purified by column chromatography over silica gel.
Biological studies
Determination of antimicrobial and antifungal activity by diffusion method in agar
Antimicrobial and antifungal activity has been studied by diffusion in agar on solid
nutrient medium (beef-extract agar for bacteria, wort agar for fungi). Petri plates con-
taining 20 mL of nutrient medium were used for all the microorganism tested. The
inoculums (the microbial loading ꢀ 109 cells (spores)/1 mL) was spread on the surface
of the solidified media and Whatman no.1 filter paper disks (6 mm in diameter)
impregnated with the test compound (0.1 and 0.5%) were placed on the plates. The dur-
ation of bacteria incubation was 24 h at 35ꢃ‘ and of fungi incubation 48–72 h at
28–30ꢃ‘. The antimicrobial effect and degree of activity of the tested compounds were
evaluated by measuring the zone diameters and the results were compared with well-
known drugs (Table 1). Every experiment was repeated three times. Parameters of
results evaluation by the method of compound diffusion in agar were given on the
Table 3.
Determination of minimal inhibitory (MIC) concentrations using serial
dilution method
The tested compounds were added to the nutrient medium (beef-extract broth for bac-
teria and wort for fungi) as solutions in dimethyl sulfoxide (DMSO) in ensuring needed
concentration (0.9–500.0 lg/mL). Bacteria and fungi inoculum was inoculated into
nutrient medium (the microbial loading was 106 cells (spores)/1 mL). The duration of
bacteria incubation was 24 h at 35ꢃ‘ and of fungi incubation 48–72 h at 28–30ꢃ‘. The
results were estimated by the microorganism growth measured by degree of microbial
turbidity in nutrient medium. Minimal inhibitory concentration (MIC) of any com-
pound is defined as the lowest concentration which completely inhibits visible growth
(turbidity on liquid nutrient medium) (Table 2).

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9
Conclusion
The aim of this study, firstly, we synthesized and characterized of novel N,S-substituted
2-nitro-1,3-butadiene compounds (4a–j and 5a–d) by using SNVin reaction in moderate
to good yields. Their structures were characterized by using the various spectroscopic
1
techniques (FT-IR, H-NMR, 13C-NMR, MS and microanalysis). These derivatives were
obtained as yellow solids or oils. We inspired by the biological importance of mono-
(S)-substituted-nitro-1,3-butadiene compounds and also nucleophilies possessing bio-
active such as piperazine, aniline, etc.
Second part of this study, the antimicrobial properties of the synthesized of new N,S-
substituted were investigated such as antibacterial and antifungal properties. The study
of synthesized compounds (4a–j and 5a–d) for their in vitro antimicrobial and antifun-
gal activity against bacteria Escherichia coli B-906, Staphylococcus aureus 209-P,
Mycobacterium luteum B-917 and fungi Candida tenuis VCM Y-70, Aspergillus niger
VCM F-1119 showed that the compound 5b has good antibacterial activity against test
culture S. aureus at concentration of 0.5% and the diameter of the inhibition zone was
15 mm using diffusion method (for vancomycin was 15 mm). Evaluation of the antifun-
gal activity using dilution method (for control compound was 15.6 lg/cm3) of the syn-
thesized N,S-substituted 2-nitrodienes showed that compounds 4c, 4d, 5b and derivative
5a had high antifungal effect against A. niger with MIC 0.9 lg/cm3 and 1.9 lg/cm3,
respectively. Therefore, we have synthesized a series of N,S-substituted-1,3-butadiene
derivatives as potential anti-Aspergillus agents.
1
Full experimental detail, H and 13C NMR spectra, MS and FTIR spectra. This mater-
ial can be found via the “Supplementary Content” section of this article’s webpage.
Funding
We gratefully thank the Research Fund of Istanbul University-Cerrahpasa for financial support of
this work [Project Numbers: FYL-2016-20351, FBA-2019-30472, FBA-2019-32783].
ORCID
Serdar Goksin Aydinli
http://orcid.org/0000-0002-2681-6011
Cigdem Sayil http://orcid.org/0000-0001-9611-3533
Nahide Gulsah Deniz
Maryna Stasevych
http://orcid.org/0000-0001-7977-7274
http://orcid.org/0000-0001-5042-4133
Viktor Zvarych
Olena Komarovska-Porokhnyavets
http://orcid.org/0000-0003-3036-0050
http://orcid.org/0000-0003-2439-481X
http://orcid.org/0000-0002-0485-8720
Volodymyr Novikov
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