Diseño, síntesis y evaluación biológica de nuevos derivados de quinoxalina y 1,4-di-n-óxido de quinoxalina con aplicación en diferentes áreas terapéuticas

Résumé

DESIGN, SYNTHESIS AND BIOLOGICAL EVALUATION OF NEW QUINOXALINE AND QUINOXALINE 1,4-di-N-OXIDE DERIVATIVES WITH APPLICATION IN DIFFERENT THERAPEUTIC AREAS Cancer is the leading cause of death in the world. Specifically, the number of deaths due to this disease are more than those due to AIDS, tuberculosis and malaria all put together; it is estimated that the number of cancer-related deaths will increase in the following years due, in part, to the growth and ageing of the population. Chronic inflammation, on the other hand, is associated with a great variety of chronic diseases such as allergy, atherosclerosis, autoimmune diseases and cancer. At present, there is a diversity of drugs which are used for the treatment of cancer and inflammation. However, their use is often limited because of the adverse effects associated to them. For this reason, new selective anticancerous and anti-inflammatory therapies are necessary in order to improve the current treatments. With this aim, this work includes the design and synthesis of thirty nine new quinoxaline and quinoxaline 1,4-di-N-oxide derivatives which have been evaluated as anticancerous, antioxidant and anti-inflammatory agents. The results obtained show that the anticancer activity of the tested compounds is due to the á,â-unsaturated ketone system and that the presence of the N-oxide groups is not essential for this biological activity. Three compounds exhibit similar or better in vivo anti-inflammatory activity than that of indomethacin, which was used as the reference drug. This means that, in the future, these compounds could very well be developed into new drugs for treating inflammatory processes.