4
Tetrahedron
respectively, when compared to the control group. In addition,
compound 4a reduced around 52, 36, 32, 27, 30 and 29 % at days
, 2, 3, 4, 5 and 6, respectively, when compared to the control
group. Besides, inhibitory effect of mycelia growth by compound
a was more efficient than 4a and 5b. Furthermore, the effect in
The lipid peroxidation assay was estimated by the
measurement of malondialdehyde (MDA) levels, which is the
2
0
1
end product of the lipid peroxidation. Compounds 1a, 5b and
3a were effective on linoleic acid peroxidation inhibition induced
by Fe-ascorbic acid at a concentration equal or superior than 50,
100 and 50 µM, respectively. According these results, 3a was the
most potent, with a IC50 value of 438 ± 67.88 µM and IMax of
51.82 ± 6.06%. Compounds 1a and 5b presented IMax of the 24.69
± 4.59 and 30.46 ± 15.29% respectively and they did not present
3
reducing the colony diameter by compound 3a was superior to 2-
bromo-ketoxime 1a at all days. This study demonstrated, for the
first time, the antifungal activity of organoselenium derivatives
on S. ampelinum.
IC50
.
Conclusion
In summary, we demonstrated the simple, efficient and
selective synthesis of novel (Z)-2-organylselanyl ketoximes. This
new class of compounds was synthesized in moderate to good
yields by the reaction of aryl or alkyl selenolate, generated in
situ, with substituted aryl and alkyl 2-bromo-ketoximes. In order
to verify the synthetic application of the synthesized 2-
(organylselanyl) ketoximes, the Beckmann rearrangement
reaction was performed and gave the corresponding acetamides
in good yields. Still, the preliminary biological studies revealed
the potential of the synthesized selanyl ketoximes against
grapevine anthracnose infection and as promising antioxidant
agents.
Figure 1. Inhibition of mycelia growth of S. ampelinum by
compounds 1a, 3a, 4a and 5b. Data are reported as mean ± S.D. of
five independent experiments. (*) Denotes p < 0.05 when compared
with the respective control for each day; (#) Denotes p < 0.05 when
compared with the compounds 1a, 4a and 5b for each day (two-way
ANOVA/Newman-Keuls).
Acknowledgments
The authors are grateful to FAPERGS (11/2026-4), CNPq
(442474/2014-8), CAPES and FINEP for the financial support.
Supplementary data
Based on the antifungal activity of 3a, and in order to explore
the pharmacological potential of this compound, we decided to
evaluate its antioxidant activity by different assays in vitro. To
Supplementary data associated with this article can be found,
in the online version, at
19
verify the influence of the selenium atom in the antioxidant
activity, compounds 1a and 5b were used as control.
References and notes
In this context, initially was carried out the 2,2-diphenyl-1-
picrylhydrazyl (DPPH) assay. The preliminary test showed that
a, which contains selenium, at 500 µM exhibited antioxidant
activity, whereas 1a (with bromine) exhibited lower activity. On
the other hand, 5b (without selenium) did not show any
antioxidant effect. The values of IMax (which represent efficacy of
compounds) was 13.90 ± 3.42% for 3a, 4.24 ± 0.65% for 1a and
2
0
1.
(a) Perin, G.; Alves, D.; Jacob, R. G.; Barcellos, A. M.; Soares, L.
K.; Lenardão, E. J. ChemistrySelect 2016, 1, 205. (b) Perin, G.;
Lenardão, E. J.; Jacob, R. G.; Panatieri, R. B. Chem. Rev. 2009,
109, 1277. (c) Freudendahl, D. M.; Shahzad, S. A.; Wirth, T. Eur.
J. Org. Chem. 2009, 1649. (d) Savegnago, L.; Vieira, A.; Seus, N.;
Goldani, B. S.; Castro, M. R.; Lenardão, E. J.; Alves, D.
Tetrahedron Lett. 2013, 54, 40. (e) Victoria, N. V.; Radatz, C. S.;
Sacchini, M.; Jacob, R. G.; Alves, D.; Savegnago, L.; Perin, G.;
Motta, A. S.; Lenardão, E. J.; Silva, W. P. Food Control. 2012, 23,
3
1
.44 ± 0.59% for 5b.
9
5. (f) Gerzson, M. F. B.; Victoria, F. N.; Radatz, C. S.; Gomes,
The 2,2-azinobis-3-ethyl-benzothiazoline-6-sulfonic acid
ABTS) assay showed that 3a, in a concentration equal or
M. G.; Boeira, S. B.; Jacob, R. G.; Alves, D.; Jesse, C. R.;
Savegnago, L. Pharmcol. Biochem. Behav. 2012, 102, 21.
2
1
(
superior than 5 µM, exhibited antioxidant activity. On the other
hand, 1a and 5b had significant effect at the concentration of 50
µM. Compound 3a presented a high potency, with IC50 values of
2.
(a) Araújo, C. R. M.; Gonsalves, A. A. Rev. Virtual Chim. 2015, 7,
1
469. (b) Sayin, U.; Yuksel, H.; Ozmen, A.; Birey, M. Radiat.
Phys. Chem. 2010, 79, 1220. (c) Milios, C. J.; Stamatatos, T. C.;
Perlepes, S. P. Polyhedron 2006, 25, 134.
Gawley, R. E. Org. React. 1988, 35, 1.
Ray, R.; Chowdhury, A. D.; Maiti, D.; Lahiri, G. K. Dalton Trans.
2014, 43, 38.
Abele, E.; Abele, R.; Golomba, L.; Visnevska, J.; Beresneva, T.;
Lukevics, E. Chem. Heteroc. Comp. 2010, 46, 905.
Sakurada, K.; Ikegaya, H.; Ohta, H.; Fukushima, H.; Akutsua, T.;
Watanabe, K. Toxicol. Lett. 2009, 189, 110.
12.75 ± 2.63 µM and a IMax of 90.18 ± 4.90%. Compounds 1a
3
4
.
.
and 5b did not inhibit 50% of the ABTS radicals and presented a
low value of IMax of the 29.21 ± 3.08 and 26.36 ± 3.43%,
respectively. The results of ABTS and DPPH assays suggest that
the mechanism of the antioxidant activity of 3a is probably based
on single electron transfer and the presence of selenium increases
the antioxidant effect.
5
6
7
.
.
.
(a) Lone, I. H.; Khan, K. Z.; Fozdar, B. I.; Hussain, F. Steroids.
2
013, 78, 945. (b) Özyürek, M.; Akpinar, D.; Bener, M.; Türkkan,
To confirm that the antioxidant mechanism of 3a involves
B.; Güçlü, K.; Apak, R. Chem. Biol. Interac. 2014, 212, 40.
Luo, Y.; Song, R.; Li, Y.; Zhang, S.; Liu, Z. J.; Fu, J.; Zhu, H. L.
Bioorg. Med. Chem. Lett. 2012, 22, 3039.
Yamazaki, K.; Terauchi, H.; Iida, D.; Fukumoto, H.; Suzuki, S.;
Kagaya, T.; Aoki, M.; Koyana, K.; Seiki, T.; Takase, K.;
Watanabe, M.; Arai, T.; Tsukahara, K.; Nagakawa, J. Bioorg.
Med. Chem. Lett. 2012, 22, 6126.
single electron transfer, the ferric ion reducing antioxidant power
8
9
.
.
2
2
(
FRAP) test was performed. In this assay 3a showed ability to
3+
reduce ions Fe from the concentration of 10 µM, while 1a and
b had an antioxidant potential at the starting concentration of 50
5
µM and 100 µM, respectively. These results are in agreement
with the ABTS assay.
1
0. (a) Abele, E.; Abele, R; Lukevics, E. Chem. Heteroc. Comp. 2009,
4
1
5, 1420. (b) Masaki, M.; Fukui, K.; Ohta, M. J. Org. Chem.
967, 32, 3564.