Perry, Maria de JesusMikiciuk-Olasik, ElżbietaBłaszczak-Świątkiewicz, KatarzynaAlmeida, Diogo Correia2017-11-032017-11-0320142013http://hdl.handle.net/10451/29594Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2014Cancer is one of the leading causes of death in the World, particularly in developing countries. Hypoxia is a characteristic present on most of those tumours, despite its variable incidence and severity within a given patient population and it is generated because solid tumour tissue is poorly perfused. There is evidence that tumours exhibiting extensive hypoxia are more aggressive than normoxic ones and, therefore they have a poorer prognosis, since hypoxia is implicated in radiotherapeutic and chemotherapeutic resistance. Currently there is a wide range of drugs to fight against tumour cells under hypoxic conditions, mainly hypoxic-activated bioreductive prodrugs, being Tirapazamine the most representative molecule of such prodrugs. In this work, a sensitive analytical method to study the stability of two new series of synthesized heterocyclic compounds, the benzimidazole-4,7-diones (5) and N-oxide benzimidazole-4,7-dione derivatives (6) was established and validated. These derivatives were developed as potential anticancer substances to be activated under hypoxic conditions. At this point we were concerned with establishing their stability in some specific environments for further in vitro studies. For that, we developed and validated an RP-UPLC method.engHypoxiaBioreductive prodrugsBenzimidazole-4,7-dioneN-oxide benzimidazole-4,7-dioneUPLCMestrado Integrado - 2014master thesis