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

M. Boiani; H. Cerecetto; M. González; M. Risso; G. Seoane; G. Sagrera; O. Ezpeleta; A. López de Ceráin; A. Monge

doi:10.3390/50300520

,

and

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.

Molecules2000, 5(3), 520-521;https://doi.org/10.3390/50300520

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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.

Figure 1.

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

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]
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]