Thiadiazoline- and Pyrazoline-Based Carboxamides and Carbothioamides: Synthesis and Inhibition against Nitric Oxide Synthase
Table 1
Structure and in vitro iNOS and nNOS inhibition (%) observed in the presence of 1 mM concentration of compounds (5a–e) and (6a–r). Pyrazoline 2a has been included as a control.
Compound
X
Y
R1
R2
R3 = R4
% iNOS inhibition
% nNOS inhibition
2a
-
-
2,3,4-(OMe)3
Ph
H
8.14 ± 1.56
62.87 ± 3.25
5a
O
S
H
Et
Me
28.09 ± 0.61
74.11 ± 1.87
5b
O
S
H
Pr
Me
58.07 ± 1.39
64.60 ± 1.50
5c
O
S
H
Ph
Me
42.06 ± 0.62
67.02 ± 0.17
5d
O
S
5-OMe
Et
Me
53.54 ± 0.23
33.3 ± 1.05
5e
O
S
5-OMe
Pr
Me
57.61 ± 1.33
26.8 ± 2.68
6a
O
CH2
5-Cl
Et
H
13.93 ± 1.92
2.27 ± 1.27
6b
O
CH2
5-Cl
Pr
H
61.97 ± 1.20
30.48 ± 2.21
6c
O
CH2
5-Cl
Ph
H
53.78 ± 2.22
16.88 ± 0.33
6d
O
CH2
5-OMe
Et
H
38.42 ± 1.61
12.79 ± 1.24
6e
O
CH2
5-OMe
Pr
H
40.68 ± 2.48
17.69 ± 1.93
6f
O
CH2
5-OMe
Ph
H
11.34 ± 1.39
22.70 ± 2.78
6g
O
CH2
4,5-(OMe)2
Et
H
44.12 ± 0.65
7.83 ± 0.90
6h
O
CH2
4,5-(OMe)2
Pr
H
47.94 ± 0.23
9.86 ± 2.60
6i
S
CH2
4,5-(OMe)2
Me
H
36.51 ± 2.15
21.61 ± 1.82
6j
S
CH2
4,5-(OMe)2
Et
H
43.56 ± 0.91
21.32 ± 1.91
6k
S
CH2
4,5-(OMe)2
Pr
H
50.92 ± 0.53
7.42 ± 1.12
6l
O
CH2
2,3,4-(OMe)3
Et
H
32.16 ± 2.03
19.97 ± 0.21
6m
O
CH2
2,3,4-(OMe)3
Pr
H
76.86 ± 0.21
31.77 ± 0.82
6n
O
CH2
2,3,4-(OMe)3
Ph
H
54.12 ± 0.23
25.88 ± 0.81
6o
S
CH2
2,3,4-(OMe)3
Me
H
57.38 ± 0.23
31.2 ± 0.42
6p
S
CH2
2,3,4-(OMe)3
Et
H
52.27 ± 0.72
38.73 ± 2.61
6q
S
CH2
2,3,4-(OMe)3
Pr
H
71.29 ± 1.53
38.82 ± 1.61
6r
S
CH2
2,3,4-(OMe)3
Ph
H
68.16 ± 1.34
47.12 ± 1.54
represent the percentage of iNOS and nNOS inhibition produced by 1 mM concentration of each compound. Each value is the mean ± SEM of three experiments performed by triplicate using recombinant iNOS and nNOS enzymes. [16].
