Month 2017
Trypanocidal Activity of Novel 5-Nitroimidazolyl O-Benzyloxime Ethers
60), 7.24–7.19 (2H, t, H-30 and H-50), 8.16 (1H, s, HC═N),
8.40 (1H, s, H4); 13C NMR (DMSO-d6, 100 MHz) δ
(ppm): 34.42 (N–CH3), 75.70 (O–CH2), 133.09 (C4),
130.86–130.80 (d, C-20 and C-60), 115.32–115.10 (d, C-30
and C-50), 140.13 (C-40), 141.04 (C-10), 142.96 (C-5),
160.76 (C-2), 163.19 (C═N); MS/ESI (m/z [M + Na]+):
301.1. Anal. Calcd for C12H11FN4O3: C, 51.80; H, 3.98;
N, 20.14. Found: C, 51.88; H, 3.97; N, 20.11.
corresponded to the concentration that led to 50% lysis of
the parasite and are summarized in Table 1.
Acknowledgments. The authors would like to thank the Brazilian
funding agencies Conselho Nacional de Desenvolvimento
Científico
e
Tecnológico (CNPq), Coordenação de
Aperfeiçoamento de Pessoal de Nível Superior (CAPES), e
Fundação Carlos Chagas Filgo de Amparo a Pesquisa do Estado
do Rio de Janeiro (FAPERJ) for financial support and for
fellowships.
(E)-1-Methyl-5-nitro-1H-imidazole-2-carbaldehyde
O-(4-
bromobenzyl) oxime (4).
Yellow solid, 65% yield, mp
141–144°C, FTIR (KBr, cmꢀ1) υmax: 1612 (C═N stretch),
1
1525 and 1367 (NO2 stretch), 1137 (CH2–O stretch); H
NMR (DMSO-d6, 400 MHz) δ (ppm): 4.03 (3H, s, N–
CH3), 5.25 (2H, s, O–CH2), 7.60–7.58 (2H, d, H-20 and H-
60), 7.40–7.38 (2H, d, H-30 and H-50), 8.16 (1H, s,
HC═N), 8.41 (1H, s, H-4); 13C NMR (DMSO-d6,
100 MHz) δ (ppm): 34.41 (N–CH3), 75.57 (O–CH2),
133.08 (C-4), 130.63 (C-20 and C-60), 131.33 (C-30 and C-
50), 129.59 (C-40), 131.55 (C-10), 136.33 (C-5), 141.21 (C-
2), 142.88 (C═N); MS/ESI (m/z [M + Na]+): 361.1 and
362.1. Anal. Calcd for C12H11BrN4O3: C, 42.50; H, 3.27;
N, 16.52. Found: C, 42.59; H, 3.26; N, 20.08.
REFERENCES AND NOTES
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(E)-1-Methyl-5-nitro-1H-imidazole-2-carbaldehyde
methylbenzyl) oxime (5).
O-(4-
Yellow solid, 80% yield, mp
116–117°C, FTIR (KBr, cmꢀ1
)
υmax 1615 (C═N
:
stretch), 1525 and 1371 (NO2 stretch), 1134 (CH2–O
1
stretch); H NMR (DMSO-d6, 400 MHz) δ (ppm): 2.30
(3H, s, Ph–CH3), 4.04 (3H, s, NCH3), 5.21 (2H, s, O–
CH2), 7.32–7.30 (2H, d, H-20 and H-60), 7.20–7.18
(2H, d, H-30 and H-50), 8.15 (1H, s, HC═N), 8.37 (1H,
s, H-4); 13C NMR (DMSO-d6, 100 MHz) δ (ppm):
20.73 (Ph–CH3), 34.40 (N–CH3), 76.46 (O–CH2),
133.08 (C-4), 128.64 (C-20 and C-60), 128.92 (C-30 and
C-50), 137.46 (C-40), 133.01 (C-10), 140.09 (C-5),
140.79 (C-2), 143.02 (C═N); MS/ESI (m/z [M + Na]+):
296.9. Anal. Calcd for C13H14N4O3: C, 56.93; H, 5.14;
N, 20.43. Found: C, 56.86; H, 5.15; N, 20.49.
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Trypanocidal activity.
The trypanocidal profile of the
new 5-nitroimidazoleO-benzyloximes derivatives (1–5) was
carried out using the trypomastigote forms of T. cruzi
obtained from mice intraperitoneally inoculated with
3 × 105 parasites of the Y strain [22]. Stock solutions of the
compounds were prepared in DMSO, and the assays were
performed in Dulbecco’s modified Eagle medium. The final
concentration of the solvent never exceeded 0.5%, which
has no deleterious effect on the parasite. All tests were
performed by mixing 100 μL of cell suspension with an
equal volume of the desired test-compound solution to
make a final drug concentration ranging from 1.5 to
200 μM and incubating at 37°C for 24 h. Untreated and
benznidazole-treated parasites were used as controls. The
results were analyzed by plotting % lysis of T. cruzi against
the concentration of the test compound. The values of IC50
[18] Data were collected at 100(2) K with Mo–Ka radiation by
means of a Rigaku Saturn724+ (2 × 2 bin mode) of the NCS crystallo-
graphic service, based at the University of Southampton, England. Data
collection, data reduction, and unit cell refinement were achieved with
CrystalClear-SM Expert 3.1 b27 [19a]. Correction for absorption was
achieved by an empirical absorption correction. The program MERCURY
[19b] were used in the preparation of the figures. SHELXL97 [19c] and
PLATON [19d] were used in the calculation of molecular geometry. The
structures were solved by direct methods using SHELXS-97 [19c] and
fully refined by means of the program SHELXL-97 [19c]. Difference
map peak provided position for the methylene hydrogen H(6). All other
hydrogen atoms were placed in calculated positions and refined with a rid-
ing model.
[19] (a) CrystalClear-SM Expert. Rigaku Corporation, Tokyo,
Japan. 2011; (b) MERCURY 3.3.8. Cambridge Crystallographic Data
Centre, UK; (c) Sheldrick, G. M. Acta Crystallogr 2008, A64, 112; (d)
Spek, A. L. Appl Crystallogr 2003, 36, 7.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet