| Author | Fonseca-Berzal, Cristina | |
| Author | Ibañez-Escribano, Alexandra | |
| Author | Reviriego, Felipe | |
| Author | Cumella, José | |
| Author | Morales, Paula | |
| Author | Jagerovic, Nadine | |
| Author | Nogal-Ruiz, Juan José | |
| Author | Escario, José Antonio | |
| Author | Silva, Patricia Bernardino da | |
| Author | Soeiro, Maria de Nazaré C. | |
| Author | Gomez-Barrio, Alicia | |
| Author | Arán, Vicente J. | |
| Access date | 2016-06-02T13:35:27Z | pt_BR |
| Access date | 2016-06-03T12:34:11Z | |
| Available date | 2016-06-02T13:35:27Z | pt_BR |
| Available date | 2016-06-03T12:34:11Z | |
| Document date | 2016 | |
| Citation | FONSECA-BERZAL, Cristina; et al. Antichagasic and trichomonacidal activity of 1-substituted 2-benzyl-5-nitroindazolin-3-ones and 3-alkoxy-2-benzyl-5-nitro-2H-indazoles. European Journal of Medicinal Chemistry, v.115, p.295-310, June 2016, | pt_BR |
| ISSN | 0223-5234 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/14416 | |
| Language | eng | pt_BR |
| Publisher | Elsevier | pt_BR |
| Rights | restricted access | |
| Subject in Portuguese | Trypanosoma cruzi | pt_BR |
| Subject in Portuguese | Medicamentos Antiprotozoários | pt_BR |
| Title | Antichagasic and trichomonacidal activity of 1-substituted 2-benzyl- 5-nitroindazolin-3-ones and 3-alkoxy-2-benzyl-5-nitro-2Hindazoles | pt_BR |
| Type | Article | |
| DOI | 10.1016/j.ejmech.2016.03.036 | pt_BR |
| Abstract | Two series of new 5-nitroindazole derivatives, 1-substituted 2-benzylindazolin-3-ones (6-29, series A) and 3-alkoxy-2-benzyl-2H-indazoles (30-37, series B), containing differently functionalized chains at position 1 and 3, respectively, have been synthesized starting from 2-benzyl-5-nitroindazolin-3-one 5, and evaluated against the protozoan parasites Trypanosoma cruzi and Trichomonas vaginalis, etiological agents of Chagas disease and trichomonosis, respectively. Many indazolinones of series A were efficient against different morphological forms of T. cruzi CL Brener strain (compounds 6, 7, 9, 10 and 19-21: IC50 = 1.58-4.19 μM for epimastigotes; compounds 6, 19-21 and 24: IC50 = 0.22-0.54 μM for amastigotes) being as potent as the reference drug benznidazole. SAR analysis suggests that electron-donating groups at position 1 of indazolinone ring are associated with an improved antichagasic activity. Moreover, compounds of series A displayed low unspecific toxicities against an in vitro model of mammalian cells (fibroblasts), which were reflected in high values of the selectivity indexes (SI). Compound 20 was also very efficient against amastigotes from Tulahuen and Y strains of T. cruzi (IC50 = 0.81 and 0.60 μM, respectively), showing low toxicity towards cardiac cells (LC50 > 100 μM). In what concerns compounds of series B, some of them displayed moderate activity against trophozoites of a metronidazole-sensitive isolate of T. vaginalis (35 and 36: IC50 = 9.82 and 7.25 μM, respectively), with low unspecific toxicity towards Vero cells. Compound 36 was also active against a metronidazole-resistant isolate (IC50 = 9.11 μM) and can thus be considered a good prototype for the development of drugs directed to T. vaginalis resistant to 5-nitroimidazoles. | pt_BR |
| Affilliation | Moncloa Campus of International Excellence (UCM-UPM & CSIC). Spain / Universidad Complutense de Madrid. Facultad de Farmacia. Departamento de Parasitologia. Madrid, Spain. | pt_BR |
| Affilliation | Moncloa Campus of International Excellence (UCM-UPM & CSIC). Spain / Universidad Complutense de Madrid. Facultad de Farmacia. Departamento de Parasitologia. Madrid, Spain | pt_BR |
| Affilliation | Moncloa Campus of International Excellence (UCM-UPM & CSIC). Spain / Consejo Superior de Investigaciones Científicas (CSIC). Instituto de Química Médica (IQM). Madrid, Spain. | pt_BR |
| Affilliation | Consejo Superior de Investigaciones Científicas (CSIC). Instituto de Química Médica (IQM). Madrid, Spain. | pt_BR |
| Affilliation | Consejo Superior de Investigaciones Científicas (CSIC). Instituto de Química Médica (IQM). Madrid, Spain. | pt_BR |
| Affilliation | Consejo Superior de Investigaciones Científicas (CSIC). Instituto de Química Médica (IQM). Madrid, Spain. | pt_BR |
| Affilliation | Moncloa Campus of International Excellence (UCM-UPM & CSIC). Spain / Universidad Complutense de Madrid. Facultad de Farmacia. Departamento de Parasitologia. Madrid, Spain. | pt_BR |
| Affilliation | Moncloa Campus of International Excellence (UCM-UPM & CSIC). Spain / Universidad Complutense de Madrid. Facultad de Farmacia. Departamento de Parasitologia. Madrid, Spain. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Moncloa Campus of International Excellence (UCM-UPM & CSIC). Spain / Universidad Complutense de Madrid. Facultad de Farmacia. Departamento de Parasitologia. Madrid, Spain. | pt_BR |
| Subject | Antiprotozoal drug | pt_BR |
| Subject | Indazole | pt_BR |
| Subject | Nitroheterocycle | pt_BR |
| Subject | Antiprotozoal drug | pt_BR |
| e-ISSN | 1768-3254 | pt_BR |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
