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