Next Article in Journal
Approach to the A-B Ring System of Forskolin through Biotransformation of Toluene
Previous Article in Journal
Analysis by Mass Spectrometry of the Polar Lipids from the Cellular Membrane of Thermophilic Lactic Acid Bacteria
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Abstract

Chemical Modifications of 1,2,5-Oxadiazole N-Oxide System Searching for Cytotoxic Selective Hypoxic Drugs

1
Cátedra de Química Orgánica, Facultad de Química, Universidad de la República , CC 1157, CP 11800, Montevideo, Uruguay
2
Laboratorio de Química Orgánica, Facultad de Ciencias, Universidad de la República , CC 1157, CP 11800, Montevideo, Uruguay
3
C.I.F.A., Universidad de Navarra, Pamplona, Spain
*
Author to whom correspondence should be addressed.
Molecules 2000, 5(3), 520-521; https://doi.org/10.3390/50300520
Published: 22 March 2000

Abstract

:
New analogues of 3-Formyl-4-phenyl-1,2,5-oxadiazole N-oxide (1) are prepared and evaluated as cytotoxic selective agents in hypoxia.

Introduction

As part of our research project on biorreducible drugs in hypoxia conditions, we have developed a series of compound derivatives of N-oxide of 1,2,5-oxadiazoles system. They were evaluated as cyto- toxic agents against V79 cells in oxia and hypoxic conditions. None of them showed selectivity in hy- poxic conditions, but the derivative 1 presented a good profile of Cytotoxicity (Figure 1). In order to gain insight the mechanism of action and to obtain a selective compound, we designed the following modifications.

Experimental

Following, we showed the modifications outlined.
All the products were characterized by 1H RMN, 13C RMN, (1D, 2D), EM, IR and in same cases elemental microanalysis. The cytotoxicity of the synthesized products was tested against V79 cells in oxia and hipoxia conditions at a concentration of 20 µM, following a protocol previously described [1].

Results and Discussion

All the synthetic procedures conducted to the products of interest with variable yields. As the drug- modulations previously described [2], the new ones may asseverate that the substituent at the 3 posi- tion of the 1,2,5-oxadiazol N-oxide plays an important role in the cytotoxic activity of this kind of compounds.

Acknowledgment:

C.H.L.C.C., CYTED, PEDECIBA.

References and Notes

  1. Monge, A.; López de Ceráin, A.; Ezpeleta, O.; Cerecetto, H.; Dias, E.; Di Maio, R.; González, M.; Onetto, S.; Seoane, G.; Suescun, L.; Mariezcurrena, R. Synthesis and Biological Evaluation of 1,2,5-Oxadiazole N-oxide Derivatives as Hypoxia-selective Cytotoxins. Pharmazie 1998, 53(11), 758–764. [Google Scholar] [PubMed]
  2. Cerecetto, H.; González, M.; Risso, M.; Seoane, G.; Ezpeleta, O.; López de Cérain; Monge, A. Derivados del Sistema N-Óxido de 1,2,5-oxadiazol como Agentes Citotóxicos Selectivos en Hy- poxia. Fármaco-modulaciones y Estudio del Mecanismo de Acción; VIII Congreso Argentino de Farmacia y Bioquímica Industrial: Buenos Aires, Argentina, junio, 1999; p. 171. [Google Scholar]
Figure 1.
Figure 1.
Molecules 05 00520 g001
Figure 2. Conditions: (a) NH2OH.HCl/p-TsOH/EtOH; (b) SOCl2/DMF; (c) NaN3/NH4Cl/DMF; (d) Ph3P+CH2OCH3 Cl-; (e) H3O+.
Figure 2. Conditions: (a) NH2OH.HCl/p-TsOH/EtOH; (b) SOCl2/DMF; (c) NaN3/NH4Cl/DMF; (d) Ph3P+CH2OCH3 Cl-; (e) H3O+.
Molecules 05 00520 g002

Share and Cite

MDPI and ACS Style

Boiani, M.; Cerecetto, H.; González, M.; Risso, M.; Seoane, G.; Sagrera, G.; Ezpeleta, O.; López de Ceráin, A.; Monge, A. Chemical Modifications of 1,2,5-Oxadiazole N-Oxide System Searching for Cytotoxic Selective Hypoxic Drugs. Molecules 2000, 5, 520-521. https://doi.org/10.3390/50300520

AMA Style

Boiani M, Cerecetto H, González M, Risso M, Seoane G, Sagrera G, Ezpeleta O, López de Ceráin A, Monge A. Chemical Modifications of 1,2,5-Oxadiazole N-Oxide System Searching for Cytotoxic Selective Hypoxic Drugs. Molecules. 2000; 5(3):520-521. https://doi.org/10.3390/50300520

Chicago/Turabian Style

Boiani, M., H. Cerecetto, M. González, M. Risso, G. Seoane, G. Sagrera, O. Ezpeleta, A. López de Ceráin, and A. Monge. 2000. "Chemical Modifications of 1,2,5-Oxadiazole N-Oxide System Searching for Cytotoxic Selective Hypoxic Drugs" Molecules 5, no. 3: 520-521. https://doi.org/10.3390/50300520

Article Metrics

Back to TopTop