ABSTRACT
Twelve novel benzimidazole derivatives were synthesized and their in vitro activities against epimastigotes of Trypanosoma cruzi were evaluated. Two derivatives (6 and 7), which have 4-hydroxy-3-methoxyphenyl moiety in their structures, proved to be the most active in inhibiting the parasite growth. Compound 6 showed a trypanocidal activity higher than benznidazole (IC50=5µM and 7.5µM, respectively) and less than nifurtimox (IC50=3.6µM). In addition, the ability of 6 and 7 to modify the redox homeostasis in T cruzi epimastigote was studied; cysteine and glutathione increased in parasites exposed to both compounds, whereas trypanothione only increased with 7 treatment. These results suggest that the decrease in viability of T. cruzi may be attributed to the change in cellular redox balance caused by compound 6 or 7. Furthermore, compounds 6 and 7 showed CC50 values of 160.64 and 160.66µM when tested in mouse macrophage cell line J774 and selectivity indexes (macrophage/parasite) of 32 and 20.1, respectively.
Subject(s)
Benzimidazoles/pharmacology , Homeostasis/drug effects , Hydrazines/pharmacology , Trypanocidal Agents/pharmacology , Trypanosoma cruzi/drug effects , Animals , Benzimidazoles/chemical synthesis , Benzimidazoles/chemistry , Dose-Response Relationship, Drug , Hydrazines/chemical synthesis , Hydrazines/chemistry , Mice , Molecular Structure , Oxidation-Reduction , Structure-Activity Relationship , Trypanocidal Agents/chemical synthesis , Trypanocidal Agents/chemistry , Trypanosoma cruzi/growth & development , Trypanosoma cruzi/metabolismABSTRACT
Se trata de un hombre de 33 años, que presentó coccidioidomicosis diseminada con pericarditis, manifestando datos de insuficiencia cardiaca. Desarrolló derrame pericárdico que progresó hacia pericarditis constrictiva. Se realizó pericardiectomía y resección de pericardio. El examen microscópico identificó numerosas esférulas de Coccidioides immitis. El paciente falleció en el postoperatorio inmediato. Este es el segundo caso de coccidioidomicosis diseminada con pericarditis, reportado en la literatura médica mexicana.