Exploring the potential activity spectrum of two 5-nitroindazolinone prototypes on different Trypanosoma cruzi strains

dc.creatorFonseca-Berzal, Cristina
dc.creatorSilva, Patricia Bernardino da
dc.creatorSilva, Cristiane França
dc.creatorVasconcelos, Mariane
dc.creatorBatista, Marcos Meuser
dc.creatorEscario, José A.
dc.creatorArán, Vicente J.
dc.creatorGómez-Barrio, Alicia
dc.creatorSoeiro, Maria de Nazaré C.
dc.date2016-03-22T17:27:09Z
dc.date2016-03-22T17:27:09Z
dc.date2015
dc.date.accessioned2023-09-26T20:25:53Z
dc.date.available2023-09-26T20:25:53Z
dc.identifierFONSECA-BERZAL, Cristina; et al. Exploring the potential activity spectrum of two 5-nitroindazolinone prototypes on different Trypanosoma cruzi strains. Parasitology Open, v.1, e1, 10p, 2015.
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/13247
dc.identifier:10.1017/pao.2015.4
dc.identifier2055-7094
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8856745
dc.descriptionIn the present study, the potential activity of two 5-nitroindazole derivatives previously proposed as suitable antichagasic prototypes was further evaluated on diverse Trypanosoma cruzistrains belonging to two discrete typing units (DTUs) frequently associated with human infection (i.e. DTUs TcII and TcVI). The trypanocidal profile that both 2-benzyl-1-propyl (22) and 2-benzyl-1-butyl (24) derivatives achieved on Tulahuen amastigotes (IC50 = 3·56 ± 0·99 and 6·31 ± 1·04 µM, respectively) correlates with that of formerly obtained on CL Brener, corroborating an outstanding activity on DTU TcVI parasites. Moreover, a sequential screening on extracellular and intracellular stages of T. cruzi Y (DTU TcII) demonstrated also the effectiveness of 22 and 24 over this strain on a similar range of activity (IC50 epimastigotes = 3·55 ± 0·47 and 7·92 ± 1·63 µM, IC50 amastigotes = 2·80 ± 0·46 and 9·02 ± 5·26 µM, respectively). These results, supported by a lack of toxicity registered over either L929 fibroblasts or primary cultures of cardiomyocytes, confirm that 5-nitroindazolinones 22 and 24 display great selectivity on both drug-sensitive (CL and Tulahuen) and drug-moderately resistant (Y) T. cruzi strains, and therefore, represent an important outcome in the research of Chagas disease chemotherapy.
dc.formatapplication/pdf
dc.languageeng
dc.publisherCambridge University Press
dc.rightsopen access
dc.subjectChagas disease
dc.subjectTrypanosoma cruzi
dc.subject5-nitroindazolinone
dc.subjectDTU
dc.subjectL929 fibroblasts
dc.subjectCardiomyocytes
dc.subjectDoença de Chagas
dc.subjectTrypanosoma cruzi
dc.subjectMiócitos Cardíacos
dc.subjectFibroblastos
dc.titleExploring the potential activity spectrum of two 5-nitroindazolinone prototypes on different Trypanosoma cruzi strains
dc.typeArticle


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