RESUMO
BACKGROUND: Chagas disease and cutaneous leishmaniasis, two parasitic diseases caused by Trypanosoma cruzi (T. cruzi) and Leishmania mexicana (L. mexicana), respectively, have a major global impact. Current pharmacological treatments for these diseases are limited and can cause severe side effects; thus, there is a need for new antiprotozoal drugs. METHODS: Using molecular docking, this work describes a structure-based virtual screening of an FDA-approved drug library against Trypanosoma cruzi and Leishmania mexicana glycolytic enzyme triosephosphate isomerase (TIM), which is highly conserved in these parasites. The selected compounds with potential dual inhibitory activity were tested in vitro to confirm their biological activity. RESULTS: The study showed that five compounds: nilotinib, chlorhexidine, protriptyline, cyproheptadine, and montelukast, were more active against T. cruzi, than the reference drugs, nifurtimox and benznidazole while chlorhexidine and protriptyline were the most active against L. mexicana. CONCLUSIONS: The analysis of these compounds and their structural characteristics may provide the basis for the development of new antiprotozoal agents.
Assuntos
Antiprotozoários , Doença de Chagas , Leishmaniose Cutânea , Trypanosoma cruzi , Humanos , Simulação de Acoplamento Molecular , Clorexidina/farmacologia , Clorexidina/uso terapêutico , Protriptilina/farmacologia , Protriptilina/uso terapêutico , Doença de Chagas/tratamento farmacológico , Leishmaniose Cutânea/tratamento farmacológico , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Antiprotozoários/químicaRESUMO
Se describe el caso de un paciente de 39 años de edad con obesidad extrema e hipoventilación alveolar, asociada a apnea obstructiva durante el sueño. Se discuten las características clínicas principales además de los procedimientos diagnósticos empleados para su diferenciación con otros síndromes de hipoventilación (Apnea del sueño, hipoventilación alveolar primaria). Se hace referencia al tratamiento farmacológico y no farmacológico más adecuando para estos pacientes