General responses to the anti-inflammatory, analgesic and anti-pyretic activities of the individual chemicals are enumerated in the table below.
|
Code
|
IUPAC Names of the Compounds
|
Anti-inflammatory activity
|
Analgesic activity
|
Anti-pyretic activity
|
1
|
349
|
4,6-Dimethoxy-2,3-diphenyl-1H-indole
|
×
|
×
|
×
|
2
|
364
|
4,6-Dimethoxy-2,3-diphenyl-1H-indole-7-carbaldehyde
|
×
|
×
|
×
|
3
|
382
|
N-Phenyl (4,6-dimethoxy-2,3-diphenyl-1H-indol-7-yl)methanimine
|
×
|
×
|
×
|
4
|
384
|
N-(3´-Chlorophenyl) (4,6-dimethoxy-2,3-diphenyl-1H-indol-7-yl)methanimine
|
×
|
×
|
×
|
5
|
4a-ll
|
N-(4´-Methylphenyl) (4,6-dimethoxy-2,3-diphenyl-1H-indol-7-yl)methanimine
|
ǂǂ
|
Aǂǂ
|
Pǂǂ
|
6
|
385
|
N-(2´,3´-Dichlorophenyl) (4,6-dimethoxy-2,3-diphenyl-1H-indol-7-yl)methanimine
|
×
|
×
|
×
|
7
|
3a-ll
|
N-(4´-Chlorophenyl) (4,6-dimethoxy-2,3-diphenyl-1H-indol-7-yl)methanimine
|
ǂǂ
|
Aǂǂ
|
Pǂǂ
|
8
|
387
|
N-(3´-Methylphenyl) (4,6-dimethoxy-2,3-diphenyl-1H-indol-7-yl)methanimine
|
×
|
×
|
×
|
9
|
388
|
N-(2´,3´-Dimethylphenyl) (4,6-dimethoxy-2,3-diphenyl-1H-indol-7-yl)methanimine
|
×
|
×
|
×
|
10
|
389
|
N-(4´-Methoxyphenyl) (4,6-dimethoxy-2,3-diphenyl-1H-indol-7-yl)methanimine
|
¥
|
¶
|
ð
|
11
|
390
|
N-(3´,4´,5´-Trimethoxyphenyl) (4,6-dimethoxy-2,3-diphenyl-1H-indol-7-yl)methanimine
|
×
|
×
|
×
|
12
|
392
|
N-(3´-Nitrophenyl) (4,6-dimethoxy-2,3-diphenyl-1H-indol-7-yl)methanimine
|
¥
|
¶
|
ð
|
13
|
21-a
|
4,5,6-Trimethoxy-2,3-diphenyl-7-phenylaminomethyl-1H-indole
|
×
|
×
|
×
|
14
|
21-b
|
4,5,6-Trimethoxy-7-(3´-methylphenylaminomethyl)-2,3-diphenyl-1H-indole
|
×
|
×
|
×
|
15
|
21-c
|
4,5,6-Trimethoxy-7-(4´-methylphenylaminomethyl)-2,3-diphenyl-1H-indole
|
×
|
×
|
×
|
16
|
21-d
|
4,5,6-Trimethoxy-7-(4´-methoxyphenylaminomethyl)-2,3-diphenyl-1H-indole
|
×
|
×
|
×
|
17
|
21-e
|
7-(3´-Chlorophenylaminomethyl)-4,5,6-trimethoxy-2,3-diphenyl-1H-indole
|
×
|
×
|
×
|
18
|
21-f
|
7-(4´-Chlorophenylaminomethyl)-4,5,6-trimethoxy-2,3-diphenyl-1H-indole
|
×
|
×
|
×
|
19
|
21-g
|
7-(3´,4´-Dichlorophenylaminomethyl)-4,5,6-trimethoxy-2,3-diphenyl-1H-indole
|
×
|
×
|
×
|
20
|
21-h
|
4,5,6-Trimethoxy-7-(3´-nitrophenylaminomethyl)-2,3-diphenyl-1H-indole
|
×
|
×
|
×
|
21
|
21-i
|
4,5,6-Trimethoxy-7-(4´-nitrophenylaminomethyl)-2,3-diphenyl-1H-indole
|
×
|
×
|
×
|
22
|
21-j
|
7-(3´-Bromophenylaminomethyl)-4,5,6-trimethoxy-2,3-diphenyl-1H-indole
|
×
|
×
|
×
|
23
|
21-k
|
7-(4´-Bromophenylaminomethyl)-4,5,6-trimethoxy-2,3-diphenyl-1H-indole
|
×
|
×
|
×
|
24
|
21-L
|
4,5,6-Trimethoxy-7-(3´,4´-dimethylphenylaminomethyl)-2,3-diphenyl-1H-indole
|
×
|
×
|
×
|
Table.1 n=5 (five animals were used for each above mentioned activity), ×: no activity, ¥: pro-inflammatory, ¶: pain intensifier (anti-analgesic), ð: pyretic (increases body temperature), ǂǂ: anti-inflammatory, Aǂǂ: analgesic, Pǂǂ: anti-pyretic
There are twenty four synthetic indole derivatives which were used in this study to check their anti-inflammatory, analgesic and anti-pyretic potential by using different appropriate methods for each activity in albino mice. From this list of chemicals, majority of derivatives have shown null potential in all of three activities, 2 chemicals 389(N-(4´-Methoxyphenyl) (4,6-dimethoxy-2,3-diphenyl-1H-indol-7-yl)methanimine) and 392(N-(3´-Nitrophenyl) (4,6-dimethoxy-2,3-diphenyl-1H-indol-7-yl)methanimine) have shown pyretic, anti-analgesic and inflammatory effects and only two chemicals 3a-II(N-(4´-Chlorophenyl) (4,6-dimethoxy-2,3-diphenyl-1H-indol-7-yl)methanimine) and 4a-II(N-(4´-Methylphenyl) (4,6-dimethoxy-2,3-diphenyl-1H-indol-7-yl)methanimine)have given the desired effects like anti-inflammatory, analgesic and anti-pyretic.
Carrageenan induced paw edema in mice
As shown in the table below administration of 10mg/kg of both the 3a-II and 4a-II and the indomethacin (10mg/kg) have prominently reduced paw edema with in 60min after the first injection as compared to the NC group which took 80min for the paw edema to subside.
Sr.no
|
Chemical code:
|
Effect
|
Time to subside paw edema
|
1
|
Control
|
Nil
|
180min
|
2
|
Indomethacin
|
Anti-inflammatory
|
90min
|
3
|
3a-ll
|
Anti-inflammatory
|
80min
|
4
|
4a-ll
|
Anti-inflammatory
|
85min
|
Table:2-Effect of test chemicals on carrageenan-induced paw edema
Anti-pyretic activity:
The two chemicals (3a-II and 4a-II) shown antipyretic activity almost parallel to Paracetamol as enumerated in the table below
Sr.
No
|
Groups
|
Before yeast
|
After 18hr
|
Temperature after treatment
|
1hr
|
2hr
|
3hr
|
1
|
Control
|
37.88±0.1a
|
38.5±.1a
|
38.2±.02a
|
38.4±.1b
|
38.4±.03c
|
2
|
Paracetamol
|
37.97±.1a
|
38.6±.01a
|
38.3±.1a
|
38.1±.1a
|
38±.02b
|
3
|
3a-II
|
37.9±.1a
|
38.5±.1a
|
38.2±.1a
|
38.1±.03a
|
38±.02ab
|
4
|
4a-II
|
37.8±.4a
|
38.5±.1a
|
38.3±.1a
|
38.2±.02a
|
38.1±.02b
|
Table: 3-Statistical analysis (ANOVA: two factors), group means ±SEM,a b c d : Anyone two groups not sharing a lower case letters differ significantly from each other
Analgesic activity:
As shown in the table administration of indomethacin (10mg/kg) has significantly extended the time threshold at 60 and 90min but after 90min there is found the same trend of decline in time threshold like all other groups control, 3a-II and 4a-II chemicals at 30, 60, 90,120 and 180min by comparing them with 0min (standard timing).
The results of analgesic activity are shown in following table
Sr.no
|
Groups
|
0 min
|
30 min
|
60 min
|
90 min
|
120 min
|
180 min
|
1
|
Control
|
5.67±.57a
|
5.23±.68a
|
4.74±.34a
|
4.37±.47a
|
4.16±.62a
|
4.02±.54a
|
2
|
Indomethacin
|
5.97±.84a
|
5.92±.46a
|
6.44±.08a
|
6.81±.75a
|
5.76±.87a
|
5.59±.70a
|
3
|
3a-II
|
8.33±.57a
|
8.33±.57a
|
6.67±.57a
|
6±.00a
|
6±.00a
|
5.67±.57a
|
4
|
4a-II
|
6.33±.57a
|
6±.00a
|
6±.57a
|
5.33±.57a
|
4.67±.57a
|
4±.00a
|
Table:4- Data is expressed as mean ±SD of n=5. *P˂0.05 compared with control. SD: Standard deviation
*0min: initial response of animals before administration of any treatment (NT) No treatment;*30, 60,…..180min: response of animal after 30, 60,….180min of administration of treatment