In vitro antimicrobial activity and in silico activity of 1-thiocarbamoyl substituted pyrazole derivatives

Article abstract of DOI:10.14233/ajchem.2018.20992

A convenient synthesis of 1-thiocarbamoyl-3-phenyl-5-diphenyl-4,5-dihydro-(1H)-pyrazole derivatives (2a-2g) was carried out by the condensation reaction of (E)-3-(phenyl)-1-(biphenyl-2-yl)-3-arylprop-2-en-1-ones (1a-1g) with thiosemicarbazide, sodium hydr

Full text of DOI:10.14233/ajchem.2018.20992

Asian Journal of Chemistry; Vol. 30, No. 4 (2018), 783-789
A
SIAN
J
OURNAL OF HEMISTRY
C
https://doi.org/10.14233/ajchem.2018.20992
in vitro Antimicrobial Activity and in silico Activity of
1-Thiocarbamoyl Substituted Pyrazole Derivatives
1
1,*
1
2
RAJA CHINNAMANAYAKAR , M.R. EZHILARASI , B.PRABHA and KULANDHAIVEL
1Department of Chemistry, Karpagam Academy of Higher Education, Eachanari, Coimbatore-641 021, India
2Department of Microbiology, Karpagam Academy of Higher Education, Eachanari, Coimbatore-641 021, India
*Corresponding author: E-mail: ezhilarasi.au@gmail.com
Received: 21 August 2017;
Accepted: 24 October 2017;
Published online: 28 February 2018;
AJC-18784
A convenient synthesis of 1-thiocarbamoyl-3-phenyl-5-diphenyl-4,5-dihydro-(1H)-pyrazole derivatives (2a-2g) was carried out by the
condensation reaction of (E)-3-(phenyl)-1-(biphenyl-2-yl)-3-arylprop-2-en-1-ones (1a-1g) with thiosemicarbazide, sodium hydroxide as
a catalyst in the presence of ethanol as solvent. Further, (E)-3-(phenyl)-1-(biphenyl-2-yl)-3-arylprop-2-en-1-ones were synthesized by the
Claisen-Schmidt condensation reaction of substituted aldehydes with 4-acetylbiphenyl in the presence of basic ethanolic solution. The
1
structure of synthesized compounds were confirmed by FT-IR, 1H NMR, 13C NMR and H-1H COSY. The antimicrobial susceptibility
tests of synthesized compounds were screened against Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli and Pseudomonas
aeruginosa. The docking studies also carried out by using 1UAG receptor for all the synthesized compounds (2a-2g).
Keywords: 4-Acetyl biphenyl chalcone, Thiosemicarbazide, Antimicrobial activity, Molecular docking studies.
interaction. Herein, the docking studies were performed for
six antimicrobial compounds with 1UAG receptor. In this receptor,
all these active sites are used to docking studies (LEU 15, THR
16, THR 36,ARG 37, GLY 73,ASN 138 and HIS 183). Finally
to evaluate the binding affinity values, types of interactions,
2D and 3D image of each compounds.
In this work, thiocarbamoyl substituted pyrazole deriva-
tives were synthesized. The skeleton structures of the synthesized
compounds confirmed by using IR, 1H and 13C NMR and 1H-
1H COSY spectral values and the screening test against Gram-
positive and Gram-negative pathogens like Staphylococcus
aureus, Streptococcuspyogenes, Escherichia coliandPseudomonas
aeruginosa.Also carried out the docking studies that have briefly
explained the structural activity relationship effectiveness of
synthesized compounds against the 1UAG protein receptor
which belongs to the origin of Escherichia coli.
INTRODUCTION
Infectious diseases caused by the bacteria and fungi are the
most serious problems in many countries. The Gram-positive
and Gram-negative pathogen are cause many infectious diseases
globally [1]. So that, we search for a novel and new microbial
resistance drugs nowadays. The morbidity is associated with
gastroenteritis of humans caused mainly by the common
pathogens like Staphylococcus, Yersinia enterocolitica and
Aeromonas hydrophila. It is one of the major threats to public
health worldwide [2]. In the synthesis of heterocyclic compounds,
chalcone is used as a intermediate and it should have a
good biological activity as well as it plays a principle role in
medicinal chemistry [3-5]. The organo-nitrogen and sulphur
compounds dominate much of synthetic, analytical and
medicinal chemistry. Several small molecules like thiadiazole,
triazole and oxadiazole based heterocycles have also been
reported to possess potential bioactivity, including antiallergic,
anticonvulsant, analgesic, anticancer, anti-microbial and anti-
inflammatory [6-9]. Thiosemicarbazides and their derivatives
exhibit good biological activities such as anticancer [10], anti-
HIV [11], antibacterial [12], antiviral [13] and antifungal [14].
The complexes of nitrogen and sulphur donor ligands are
having a special and specific effect against the pathogens such
as small pox virus, influenza, fungi and cancer [15]. The docking
studies are mainly used to understand the drug-receptor
EXPERIMENTAL
Thiosemicarbazide (25 g) was purchased from Sigma
Aldrich. The melting points of the compounds were determined
through open capillary method and values were uncorrected.
The FT-IR spectrum (cm-1) was recorded through KBr in a
Fourier transform IR spectrometer (model Shimadzu 8400s)
in the range of 4000-400 cm-1. The 1H, 13C NMR spectra and
1H-1H Cosy were recorded by Brucker 400 MHz spectrometer

784 Chinnamanayakar et al.
Asian J. Chem.
and chemical shifts are recorded in δ value (ppm) with tetra
methylsilane (TMS) as internal standard, as well as CDCl3
used as a solvent.
Molecular docking studies: The molecular docking studies
were done through the Auto Dock Tools version is 1.5.6 and
Auto dock version 4.2.5.1. The preparation of protein was done
by literature method [17].
Synthesis of (E)-3-(phenyl)-1-(biphenyl-2-yl)-3-aryl-
prop-2-en-1-one derivatives (1a-1g): 4-Acetyl biphenyl (1 mol)
and various substituted aromatic aldehydes (1 mol) were taken
in a beaker and added 30 mL of ethanol containing 2 g of NaOH
pellets. The mixture was stirred well for 30 min in an ice cold
bath, after it was poured into the crushed ice containing 500
mL beaker and this reaction mixture was kept into overnight
at room temperature. The chalcone were precipitated out as
solid. Then it was filtered, dried and recrystallized from ethanol.
The purity of the compound was checked by TLC by using
CHCl3 as a solvent.
Synthesis of 1-thiocarbamoyl-3-phenyl-5-diphenyl-4,5-
dihydro-(1H)-pyrazole derivatives (2a-2g): One equivalent
of (E)-3-(phenyl)-1-(biphenyl-2-yl)3-arylprop-2-en-1-one (1a-
1j), two equivalents of thiosemicarbazide and 30 mL ethanol
containing 3 g of NaOH solution were taken in a round bottom
flask. The reaction mixture was refluxed for 32-40 h at 60 °C.
After the completion of the reaction, the reaction mixture was
poured into crushed ice and kept overnight at room temperature
(Scheme-I). The crude product was filtered, dried and recrysta-
llized from ethanol. The purity of the compound was checked
by TLC by using petroleum ether and ethyl acetate (9:1) as a
solvent.
Antimicrobial activity: The synthesized compounds were
screened for antibacterial activity and calculate the minimal
inhibitory concentrations (MICs). The newly synthesized com-
pounds were tested against four different bacterial strains using
agar disk diffusion method. The Gram-positive bacteria strains
were Staphylococcus aureus, Staphylococcus pyogenes and
Gram-negative bacteria strains were Escherichia coli, Pseudo-
monas aeruginosa. The drug ciprofloxacin was used as stan-
dard drug and the DMSO used as the solvent control in this
activity.
Minimum inhibitory concentration (MIC): The minimum
inhibitory concentration of the synthesized compounds was
performed using broth dilution assay method. For assaying
synthesized compounds, the starting concentration was kept
at 8 mg/mL in the first tubes containing 1 mL of broth. Tubes
were vortexed to make the initial standard concentration. This
was serially diluted to other tubes and finally 1 mL was discard
from the last tube hence making the dilution of 2, 1, 0.5, 0.23
mg/mL respectively. To all these test tubes, 0.1 mL of the long
phase cultures of target microorganisms were added separately
and incubated at 37 °C for 24-48 h. The tube was examined
for visible turbidity after the incubation and plated on their
respective media incubated at 37 °C for 24 h for bacteria and
room temperature for yeast [16].
RESULTS AND DISCUSSION
The starting materials of the chalcone derivatives were
prepared from known Claisen-Schmidt condensation and to
form (E) form chalcone derivatives. Further, the chalcones were
reacted with thiosemicarbazide in the presence of base medium;
from this the thiocarbamoyl derivatives (2a-2g) were synthe-
sized. The IR, 1H, 13C NMR and 1H-1H Cosy NMR spectral results
were used to predict the chemical structure of the synthesized
compounds 2a-2g.
1-Thiocarbamoyl-3-phenyl-5-diphenyl-4,5-dihydro-
(1H)-pyrazole (2a): Yield 87 %; m.p.: 248-250 °C; yellow
solid; m.f.: C22H19N3S; IR (KBr, νmax, cm–1): Pyrazole 1587.42
(C=N), 1525.69 (C=C), 1462.04 (C-N), 3253.91, 3402.43 (N-
1
H), 3059.10 (Ar-CH), 692.44, 731.02, 759.95, 837.11; H
NMR (CDCl3), 400 MHz, δ, ppm (J, Hz): 3.27 (1H, dd, H4A,
J4A,4B = 17.6 Hz, J4A,5X = 3.6 Hz); 3.90 (1H,dd, H4B, J4B,4A = 11.2
Hz, J4B,5X = 17.6 Hz); 6.09 (1H, dd, H5X, J5X,4A= 3.4 Hz, J5X,4B
=
11.4 Hz); 7.27-7.83 (14H, m,Ar-H). 13C NMR δ; 176.75 (C=S),
155.69 (C3 of pyrazole ring), 43.14 (C4 of pyrazole ring),
63.55 (C5 of pyrazole ring); 125.43, 127.09, 127.45, 127.50,
127.69, 128.09, 128.95, 128.99 (Ar-C); 143.82, 141.78,
139.92, 129.49 (Ipso carbon).
1-Thiocarbamoyl-3-fluorophenyl-5-diphenyl-4,5-
dihydro-(1H)-pyrazole (2b): Yield 75 %; m.p.: 242-248 °C;
Yellow solid; m.f.: C22H18N3SF; IR (KBr, νmax, cm–1): Pyrazole
1572.05 (C=N), 1498.75 (C=C), 1469.82 (C-N), 3349.53,
3473.95 (N-H), 3048.62 (Ar-CH), 694.40, 730.09, 760.95,
1
833.28; H NMR (CDCl3), 400 MHz, δ, ppm, (J, Hz): 3.19
(1H, dd, H4A, J4A,4B = 18 Hz, J4A,5X=3.2 Hz); 3.93 (1H, dd, H4B,
J4B,4A=11.4 Hz, J4B,5X = 18.2 Hz); 5.94 (1H, dd, H5X, J5X,4A=3.4
Hz, J5X,4B= 11.4 Hz); 7.12-8.05 (13H, m, Ar-H).13C NMR δ;
176.03 (C=S); 42.27 (C4 of pyrazole ring); 62.28 (C5 of
pyrazole ring); 162.30 (C3 of pyrazole ring); 115.08,115.30,
126.70, 126.83, 127.38, 127.46, 127.75, 128, 129.02, 129.82
N(Ar-C); 139.11, 142.01, 154.64, 159.89 Ipso carbon).
1-Thiocarbamoyl-3-methylphenyl-5-diphenyl-4.5-
dihydro-(1H)-pyrazole (2c): Yield 81 %; m.p.: 230-238 °C;
yellow solid; m.f.: C23H21N3S; IR (KBr, νmax, cm–1): Pyrazole
1587.48 (C=N), 1513.22 (C=C), 1462.11 (C-N), 3244.41,
3431.51 (N-H), 3027.41 (Ar-CH), 651.00, 692.47, 724.30,
1
762.88. H NMR (CDCl3), 400 MHz, δ, ppm, (J, Hz): 3.25
(1H, dd, H4A, J4A,4B = 16 Hz, J4A,5X = 4 Hz); 3.88 (1H, dd, H4B,
J4B,4A = 12 Hz, J4B,5X = 20 Hz); 6.06 (1H, dd, H5X, J5X,4A = 4 Hz,
J5X,4B = 12 Hz); 2.34 (CH3 (H), S; 7.17-7.83 (13H, m, Ar-H).
S
H
N
NH2CSNHNH2
40 h refluxed
H2N
O
HC
C
Ar
N
0 °C, stirring 3 h
Ar
CHO
C
C
+
10 % NaOH
NaOH in ethanol
Ar
CH3
O
1a-1g
2a-2g
Ar = C6H5 (2a), C6H4F (2b), C6H4CH3 (2c), C6H4Br (2d), C6H4OCH3 (2e), C6H3Cl2 (2f), C6H5O (2g)
Scheme-I: Synthesis of 1-thiocarbamoyl-3-phenyl-5-diphenyl-4,5-dihydro-(1H)-pyrazole derivatives

Vol. 30, No. 4 (2018)
in vitro Antimicrobial Activity of 1-Thiocarbamoyl Substituted Pyrazole Derivatives 785
13C NMR δ; 176.68 (C=S); 155.72 (C3 of pyrazole ring); 43.18
(C4 of pyrazole ring); 63.37 (C5 of pyrazole ring); 125.39,
1227.09, 127.45, 127.49, 128.09, 129, 129.56, 129.62 (Ar-
C); 143.76, 139.94, 138.89, 137.35 (Ipso carbon).
2D NMR spectral analysis
1H-1H Cosy: The 2D 1H-1H COSY spectrum of compound
2a shows that the signal at 3.27 ppm has one bond correlation
with the doublet of doublet signals at 3.90 and 6.09 ppm.
Similarly the signal at 3.90 ppm has one bond correlation with
the signals at 3.27 and 6.09 ppm. The signal at 6.09 ppm has
one bond also correlation with 3.27 and 3.90 ppm. From this
observed the correlations of 2D NMR spectrum results, unambi-
guously assign that the doublet of doublets observed in the
range of 3.27, 3.90 and 6.09 ppm are due to the presence of
H4A, H4B and H5X protons, respectively.
1-Thiocarbamoyl-3-bromophenyl-5-diphenyl-4,5-
dihydro-(1H)-pyrazole (2d): Yield 73 %; m.p.: 232-236 °C;
yellow solid; m.f.: C22H18N3SBr; IR (KBr, νmax, cm–1): Pyrazole
1588.45 (C=N), 1523.83 (C=C), 1463.07 (C-N), 3258.87,
3404. 51 (N-H), 3029.34 (Ar-CH), 656.79, 692.47, 723.34,
1
765.77. H NMR (CDCl3), 400 MHz, δ, ppm, (J, Hz): 3.23
(1H, dd, H4A, J4A,4B = 16 Hz, J4A,5X = 4 Hz); 3.90 (1H, dd, H4B,
J4B,4A = 12 Hz, J4B,5X = 16 Hz); 6.04 (1H, dd, H5X, J5X,4A = 4 Hz,
J5X,4B = 12 Hz); 7.14-7.83 (13H, m, Ar-H). 13C NMR, δ, ppm;
182.91 (C=S); 49.13 (C4 of pyrazole ring; 69.19 (C5 of
pyrazole ring); 150.15 (C3 of pyrazole ring; 127.76, 133.27,
133.51, 133.63, 133.72, 134.32, 135.18, 135.43 (Ar-C); 150.15,
147.01, 146.03, 138.26 (Ipso carbon).
Docking studies
in silcoActivity: The 1UAG protein is responsible for the
mechanism of cell wall synthesis. The synthesized compounds
showed a good docking score and also have good interaction.
Especially (compound 2e) showed a good docking score (-8.4
kcal/mol) compared to other 6 compounds. Other compound
docking scores are given by decreasing order -8.3, -8.3, -8.2,
-8.1, -8.0 and -7.8 kcal/mol of 2f, 2d, 2b, 2a, 2c and 2g. The
compound 2e interacts with IUAG by forming conventional
hydrogen bonding at LYS A: 319 and PHE A: 422. Other
compounds (2f, 2d, 2b, 2a, 2c, 2g) conventional hydrogen
bonding at PHE A: 422; PHE A: 422; PHE A: 422, LYS A:
319; PHE A: 422; PHE A: 303, ARG A: 302, THR A: 297;
ASN A:138,GLU A:157, LYS A:319. The benzene ring of the
compound 2a forms the alkyl and π-alkyl interaction withALA
A: 414; π-σ interaction with LEU A: 416; π-σ interaction in
the pyrazole ring is ALA A: 414; C=S forms conventional
hydrogen bond with PHE: 422. The benzene ring of the
compounds 2b forms the π-alkyl interaction with LEUA: 416;
π-σ interaction with LEUA: 416,ALAA: 414; C=S forms the
conventional hydrogen bond with PHEA: 422. The compound
2c forms the alkyl and π-alkyl interaction with LYS A: 262;
π-σ interaction with LYSA: 262; π-π stacked interaction with
PHE A: 303. The benzene ring of the compound 2d forms the
alkyl and π-alkyl interaction withALAA: 414; π-σ interaction
with LEU A: 416; π-σ interaction in the pyrazole ring is ALA
A: 414; C=S forms the conventional hydrogen bond with PHE
A: 422. The benzene ring of the compound 2e forms the alkyl
and π-alkyl interaction with LYSA: 348, LEUA: 346; π-σ inter-
action with LEU A: 416, ALA A: 414; C=S forms the conven-
tional hydrogen bond with PHE A: 422. The benzene ring of
the compound 2f forms the alkyl and π-alkyl interaction with
LYS A: 348, ALA A: 414; π-σ interaction with LEU A: 416;
π-σ interaction in the pyrazole ring isALAA: 414; C=S forms
the conventional hydrogen bond with PHEA: 422. The benzene
ring of the compound 2g show no alkyl and π-alkyl interaction;
π-σ interaction with LEUA: 15; The π-π T-shaped interaction
with PHEA: 422; C=S forms the conventional hydrogen bond
with HISA: 183.The binding value and conventional hydrogen
bonds of the synthesized compounds are shown in Table-1.
The 2-dimensional and 3-dimensional images of the synthe-
sized compounds are shown in Fig. 1.
1-Thiocarbamoyl-3-methoxyphenyl-5-diphenyl-4,5-
dihydro-(1H)-pyrazole (2e): Yield 85 %; m.p.: 234-238 °C;
yellow solid; m.f.: C23H21N3OS; IR (KBr, νmax, cm–1): Pyrazole
1579.77 (C=N), 1509.36 (C=C), 1473. 68 (C-N), 3427.65,
3475.88 (N-H), 3053.45 (Ar-CH), 695.37, 728.16, 764.81,
1
834.25. H NMR (CDCl3), 400 MHz, δ, ppm, (J, Hz): 3.84
(1H, dd, H4A, J4A,4B = 10 Hz, J4A,5X = 7.6 Hz); 3.88 (1H, dd,
H4B, J4B,4A = 12.4 Hz, J4B,5X = 8 Hz); 6.09 (1H, dd, H5X, J5X,4A
=
11.4, J5X,4B = 4 Hz); 3.80 (3H, s, OCH3); 7.42-7.84 (13H, m,
Ar-H). 13C NMR, δ, ppm; 172.26 (C=S); 153.78 (C3 of pyrazole
ring); 50.01 (C4 of pyrazole ring; 57.82 (C5 of pyrazole ring);
109.02, 121.59, 121.83, 122.00, 122.19, 122.24, 122.63,
122.83, 123.73 (Ar-C); 150.62, 138.40, 134.74, 128.93 (Ipso
carbon).
1-Thiocarbamoyl-3-(2,3-dichlorophenyl)-5-diphenyl-
4,5-dihydro-(1H)-pyrazole (2f): Yield 72 %; m.p.: 258-262
°C; yellow solid; m.f.: C22H17N3SCl2; IR (KBr, νmax, cm–1):
Pyrazole 1591.34 (C=N), 1519.97 (C=C), 1467.89 (C-N),
3255.98, 3403.54 (N-H), 3029.34 (Ar-CH), 621.11, 699.23,
726.73, 768.67. 1H NMR (CDCl3), 400 MHz, δ, ppm, (J, Hz):
3.17 (1H, dd, H4A, J4A, 4B = 18 Hz, J4A,5X = 6 Hz); 4.01 (1H, dd,
H4B, J4B,4A = 18 Hz, J4B,5X = 10 Hz); 6.41 (1H, dd, H5X, J5X,4A
=
4 Hz, J5X,4B = 12 Hz); 7.82-7.02 (11H, m, Ar-H). 13C NMR, δ,
ppm; 176.84 (C=S); 156.01 (C3 of pyrazole ring); 41.89 (C4
of pyrazole ring); 62 (C5 of pyrazole ring); 127.08, 127.44,
127.52, 127.73, 128.15, 128.99, 129.14, 129.59 (Ar-C);
144.01, 140.01, 140.90, 139.82 (Ipso carbon).
1-Thiocarbamoyl-3-(2-hydroxyphenyl)-5-diphenyl-
4,5-dihydro-(1H)-pyrazole (2g): Yield 78 %; m.p.: 246-254
°C; yellow solid; m.f.: C22H19N3OS; IR (KBr, νmax, cm–1):
Pyrazole 1589.41 (C=N), 1521.90 (C=C), 1466.93 (C-N),
3405.47, 3357.91 (N-H), 3024.51, 3062.48 (Ar-CH), 652.90,
697.30, 727. 19, 765.77; 1H NMR (CDCl3), 400 MHz, δ, ppm,
(J, Hz): 3.16 (1 H, dd, H4A, J4A,4B = 17.8 Hz, J4A,5X = 3.8 Hz);
3.96 ppm (1H, dd, H4B, J4B,4A = 11.6 Hz, J4B,5X = 18 Hz); 6.37
(1H, dd, H5X, J5X,4A = 3.8 Hz, J5X,4B = 11.4 Hz); 7.07-7.80 (11H,
m,Ar-H). 13C NMR, δ; 176.898 (C=S), 156.00 (C3 of pyrazole
ring), 42.02 (C4 of pyrazole ring), 61.41 (C5 of pyrazole ring;
127.08, 127.28, 127.43, 127.48, 128.10, 128.82, 128.98,
129.36, 130.05 (Ar-C); 131.35, 138.64, 139.89, 143.90 (Ipso
carbon).
Antimicrobial activity: The in vitro antibacterial activities
of the synthesized compounds are subjected at different
concentrations (1.0, 0.5, 0. 25 mg/mL) are given in Table-2.
From the screening results 2a, 2d, 2f and 2g showed a good

786 Chinnamanayakar et al.
Asian J. Chem.
TABLE-1
Compd. Binding affinity
Conventional hydrogen bond
PHE A:422
Other bond
Alkyl and π-alkyl bond
No.
(Kcal/mol)
-8.1
ALA A: 414
ALA A:414, LEU A:416, LYS A:115,
LYS A:319
2a
-8.2
-8.0
PHE A:422, LYS A:319
PHE A:303, ARG A:302,
THR A:297
LEU A: 416
LYS A: 262
LEU A:416, ALA A:414
LYS A:26, LYS A: 262
2b
2c
-8.3
PHE A:422
LEU A: 416,
ALA A: 414
LYS A:115, LYS A:319, LEU A:416,
ALA A:414
2d
-8.4
-8.3
PHE A:422, LYS A: 319
PHE A:422
LYS A:348, LEU A:346
LYS A:348, LEU A:416,
ALA A:414
LEU A:416, ALA A:414
ALA A:414, LEU A: 416
2e
2f
-7.8
LYS A: 319, GLU A: 157,
ASN A: 138
–
PHE A:422, LEU A 115
2g
S
NH2
N
N
2a
S
NH2
N
N
F
2b
S
NH2
N
N
H3C
2c

Vol. 30, No. 4 (2018)
in vitro Antimicrobial Activity of 1-Thiocarbamoyl Substituted Pyrazole Derivatives 787
S
NH2
N
N
Br
2d
S
NH2
N
N
H CO
3
2e
S
NH2
N
N
CH
3
CH
2f
3
S
NH2
N
N
OH
2g
Fig. 1. 2D and 3D images of the synthesized 1-thiocarbamoyl substituted pyrazole derivatives (2a-2g)

788 Chinnamanayakar et al.
Asian J. Chem.
TABLE-2
ANTIMICROBIAL SUSCEPTIBILITY AGAINST SYNTHESIZED
1-THIOCARBAMOYL SUBSTITUTED PYRAZOLE DERIVATIVES (2a-2g)
Zone of inhibition (diameter in mm)
Compd.
No.
Staphylococcus aureus
Streptococcus pyogenes
Escherichia coli
Pseudomonas aeruginosa
1.0
0.5
0.25
1.0
0.5
0.25
1.0
0.5
0.25
1.0
0.5
0.25
mg/mL
16
14
15
16
13
16
16
mg/mL
13
11
10
11
> 10
10
15
mg/mL
> 10
10
> 10
> 10
> 10
> 10
10
mg/mL
16
18
21
19
15
12
22
mg/mL
mg/mL
10
mg/mL
mg/mL
12
11
11
15
> 10
11
14
mg/mL
10
10
10
12
> 10
> 10
14
mg/mL
20
18
16
–
10
> 10
25
mg/mL
13
15
13
–
> 10
> 10
15
mg/mL
15
12
16
14
13
11
20
17
16
18
18
13
12
24
> 10
> 10
> 10
–
> 10
–
2a
2b
2c
2d
2e
2f
≥
10
12
12
10
10
13
11
2g
TABLE-3
MINIMUM INHIBITORY CONCENTRATION OF SYNTHESIZED
1-THIOCARBAMOYL SUBSTITUTED PYRAZOLE DERIVATIVES (2a-2g)
Staphylococcus aureus
Streptococcus pyogenes
Escherichia coli
Pseudomonas aeruginosa
Compd.
No.
1.0
mg/mL
0.5
mg/mL
0.25
mg/mL
1.0
mg/mL
0.5
mg/mL
0.25
1.0
0.5
mg/mL
0.25
1.0
mg/mL
0.5
mg/mL
0.25
mg/mL
mg/mL
++
++
–
mg/mL
mg/mL
–
–
–
–
–
–
–
–
–
++
–
++
++
–
++
++
++
++
++
++
++
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
++
–
++
–
–
++
++
++
–
++
++
–
–
–
–
++
++
–
–
–
–
++
++
–
++
++
++
++
++
++
++
2a
2b
2c
2d
2e
2f
–
++
++
++
–
–
2g
The negative sign (–) indicates no growth on the plates; The positive sign (++) indicates growth on the plates.
zone of inhibition against Staphylococcus auresus (Gram-
positive); Compounds 2g exhibited a good zone of inhibition
against Streptococcus pyogenes (Gram-positive); Compounds
2g exhibited a good activity against Escherichia coli (Gram-
negative); Compounds 2g showed a good zone of inhibition
against Pseudomonas aeruginosa (Gram-negative).
The minimum inhibitory concentration of the synthesized
compounds are subjected at different concentrations (1.0, 0.5,
0.25 mg/mL) are given in Table-3. From this screening result
the compound 2c and 2d exhibit a good inhibition at minimum
concentration (0.25 mg/mL against Streptococcus pyogenes
(Gram-positive) strain. In Escherichia coli (Gram-negative),
the synthesized compound 2d and 2g shows a good inhibition
at minimum concentration (0.25 mg/mL). The compound 2a,
2b, 2d and 2g shows a good minimum inhibitory concentration
(0.5 mg/mL) against Staphylococcus aureus (Gram-positive).
The synthesized compound 2a, 2b, 2d, 2f and 2g show a good
minimum inhibitory concentration (0.5 mg/mL) against
Pseudomonas aeruginosa (Gram-negative).
The electron negativity substitution group (Br) have a good
inhibition against Streptococcus pyogenes and Escherichia coli
and the electron releasing group (CH3) have a efficient inhibition
against Streptococcus pyogenes at 0.25 mg/mL. The same bromo
substitutions have the good inhibition against Staphylococcus
aureus at 0.5 mg/mL. Including base and the other substitutions
such as fluoro have a better inhibition against Pseudomonas
aeruginosa at the concentration 0.5 mg/mL. The hydroxy group
also show a good MIC at 0.25 mg/mL against Escherichia coli
and Streptococcus pyogenes.
Conclusion
A new series of thiocarbamoyl derivatives were synthesized
and characterized by FT-IR, 1H NMR and 13C NMR techniques
and 1H-1H COSY. The synthesized compounds were screened
for antibacterial activity. From this result, the compound (2a,
2d, 2f, 2g) shows good zone of inhibition against Gram-positive
strain (Staphylococcus aureus). In the Streptococcus pyogenes
(Gram-positive strain), the studies on electron releasing group
(CH3) shows a excellent zone of inhibition; The compound
(2d, 2g) shows a good zone of inhibition against Escherichia
coli (Gram-negative strain); The compound 2g shows a good
zone of inhibition against Pseudomonas aeruginosa (Gram-
negative strain). The Br substitution exhibit a good inhibition
at 0.25 mg/mL against Streptococcus pyogenes and Escherichia
coli. It also has a better inhibition against Staphylococcus
aureus at 0.5 mg/mL. Finally the molecular docking studies
were carried out. From this prediction of the in silco activity
of the synthesized compounds against on the MurD enzymatic
proteins. Also this docking result the compound 2e shows a
good docking score (-8.4 kcal/mol) against 1UAG protein.
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