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

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.