A. Gómez-Rivera et al. / Bioorg. Med. Chem. Lett. 23 (2013) 5519–5522
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the right hind paw of the specimens was measured every hour for
h, employing the pletismometer technique.
For each animal, the Maximum Anti-inflammatory Protective Ef-
7
fect (MAPE) was calculated every hour during the length of the
experiment. MAPE was calculated as a percentage, according to
the
following
equation:MAPE(%) = [(VcarrꢀVtreat)/(VcarrꢀV
o
)]-
⁄
[100]Where:Vcarr = volume of the rear paw of the rat which re-
ceived carrageenan i.pl.Vtreat = volume of the rear paw of the rat
who received either meloxicam or chalcone prior the application
1
4
o
of carrageenan.V = volume of the rear paw of the rat at zero time.
The results for the MAPE are presented as the average ± stan-
dard deviation. In order to compare the differences between the
experimental groups, an ANOVA a Tukey Test and a Contrast Anal-
ysis were performed. Results were considered statistically signifi-
cant at p <0.05.
Figure 4 show that the oral administration of every tested
ꢀ
1
chalcone, at a single oral dose of 200 mg kg , produced an anti-
inflammatory protective effect which is time-dependent. For com-
pound 2, the maximum anti-inflammatory effect (34.8 ± 2.5%) was
obtained 3 h after the administration and the anti-inflammatory
effect was maintained in around 30% during the rest of the exper-
iment. For compound 3 the maximum effect (31.0 ± 5.6%) was
reached 2 h after the administration, but it began to diminish
one hour later to reach values near zero 7 h after the administra-
tion. For compound 4, the highest protective effect (38.0 ± 6.3%)
was reached one hour after de administration, it diminished at
around 20% 2 h after the administration and remained steady
during the next 6 h. For the reference group (compound 8) the
maximum effect (59.3 ± 3.8%) was reached within 2 h after the
administration, and remained steady (around 50–60%) during the
Figure 5. AUC for the MAPE of chalcones 5, 6 and 7 (200 mg kgꢀ1, p.o.) and the
ꢀ
1
reference drug 8 (10 mg kg , p.o.) Each bar represents the average ± standard
⁄
deviation (n = 6). Statistically significant difference (p <0.05).
7
h of the experiment.
The area under the curve (AUC) for the temporal evolution of
the anti-inflammatory protective effect of each chalcone and the
reference drug administered p.o. were also calculated and the re-
sults are presented in Figure 5. The highest AUC corresponds to
compound 5 (303.71 ± 34.32), whereas compound 6 has the lowest
AUC (137.26 ± 16.82). The Tukey Test applied for the AUC values,
showed that the differences between the AUC’s and therefore the
differences in the anti-inflammatory protective effect of each
tested chalcone, are statistically significant at p <0.05. Compound
Figure 6. Time course of the MAPE of chalcones 5, 6 and 7 (200 mg kgꢀ1, ip) and the
reference drug 8 (10 mg kg , p.o.) on the carregeenan induced paw edema in rats.
Each point represents the average ± standard deviation (n = 6).
ꢀ
1
5
(with the nitro group at the ortho position), developed the high-
est protective anti-inflammatory effect, while compound 6 (with
the nitro group at the meta position), showed the lowest protective
anti-inflammatory effect. When compared the AUC values of the
three tested chalcones versus the reference drug 8, it was found
a statistically significant difference at p <0.05, being meloxicam
the compound with the best anti-inflammatory protective effect.
On the other hand, the intraperitoneal administration of the
three nitro-substituted chalcones showed anti-inflammatory pro-
tective effects which were all time-dependent (Fig. 6). For com-
pound 5 the maximum effect (58.2 ± 3.2%) was reached 1 h after
the administration. The MAPE for 5 was maintained between 50%
and 60% during the 7 h of the experiment. Compound 6 recorded
the highest MAPE for the three chalcones (68.0 ± 3.8%) and it was
reached within the first hour of the experiment, although 5 h after
the administration. Compound 7 reached its highest MAPE 2 h
after the administration (43.2 ± 3.3%), this effect was maintained
steady along the experiment. The highest MAPE for the reference
drug 8 (59.3 ± 3.8%) was reached 2 h after the administration and
it was maintained steady during the 7 h of the experiment.
The AUC for the temporal evolution of the anti-inflammatory
protective effect of each chalcone and the reference drug adminis-
tered ip were also calculated and the results are presented in Fig-
ure 7. As occurred in the oral administration, compound 5 also
showed the highest AUC (378.08 ± 32.34), but unlike the former
procedure, it was compound 7 and not 6 the one with the smallest
AUC (246.78 ± 36.8). The application of the Tukey test over the AUC
values showed statistically significant differences when the AUC of
Figure 4. Time course of the MAPE of chalcones 5, 6 and 7 (200 mg kgꢀ1, p.o.) and
the reference drug 8 (10 mg kg , p.o.) on the carregeenan induced paw edema in
rats. Each point represents the average ± standard deviation (n = 6).
ꢀ
1