Tesis doctoral de Elsa Moreno De Viguri
Design, synthesis and study of quinoxaline-2-carboxamide 1,4-di-n-oxide derivatives as anti-tuberculosis agents tuberculosis (tb), caused by mycobacterium tuberculosis (m. Tb), is a contagious and airborne disease which chiefly affects young adults in their most productive years. Tb is a worldwide disease, although 22 countries account for 80% of the tb cases in the world. According to the world health organization, one person worldwide dies every 20 seconds from tb and it is estimated that one third of the world population is infected by m.Tb. The statistics reveal that 1.7 million people died from tb and that there were an estimated 9.4 million incident cases of tb in 2009. Moreover, the global epidemiology of drug-resistant tb is unknown and the continuing emergence of multi-drug-resistant tb will make it more difficult to control tb in the future. at present, there is a diversity of drugs which are used for the treatment of tb. Nevertheless, there is an urgent need for new and active oral drugs for the treatment of latent and active tb which could shorten the duration of the treatment and could extend the range of effective treatment options, including mdr-tb and xdr-tb. with this objective in mind, this work includes the design and synthesis of forty-seven new quinoxaline-2-carboxamide 1,4-di-n-oxide derivatives which have been evaluated as anti-tuberculosis agents within the anti-tuberculosis programs developed by the national institute of allergy and infectious diseases. thirty-nine of the eighty-eight evaluated compounds were considered active against m.Tb h37rv and evaluated in a cytotoxicity assay in vero cells. Twenty-four of the derivatives showed interesting selectivity index values and two of them presented selectivity index values in the same range as the reference drug rifampicin. a reversed-phase high performance liquid chromatography method was set up for the experimental determination of the octanol-water partition coefficients for the dioxidized quinoxaline derivatives. Nevertheless, it was not possible to establish a relationship between said values and the anti-tuberculosis activity of the compounds. moreover, thirty-seven derivatives were included in an electrochemical study to investigate the reduction potentials of quinoxaline 1,4-di-n-oxide derivatives. The relationship found between the electrochemical behavior and the anti-tuberculosis activity of the compounds corroborates the hypothesis that this type of derivatives can be activated by bio-reduction, generating more active species. these results suggest that these compounds should be considered for further testing in order to be developed into new drugs for treating tb.
Datos académicos de la tesis doctoral «Design, synthesis and study of quinoxaline-2-carboxamide 1,4-di-n-oxide derivatives as anti-tuberculosis agents«
- Título de la tesis: Design, synthesis and study of quinoxaline-2-carboxamide 1,4-di-n-oxide derivatives as anti-tuberculosis agents
- Autor: Elsa Moreno De Viguri
- Universidad: Navarra
- Fecha de lectura de la tesis: 17/06/2011
Dirección y tribunal
- Director de la tesis
- Antonio Monge Vega
- Tribunal
- Presidente del tribunal: ignacio Aldana moraza
- víctor Martínez merino (vocal)
- julia Castro pichel (vocal)
- mauro Ravera (vocal)