Synthesis, biological evaluation and chemometric analysis of indazole derivatives. 1,2-Disubstituted 5-nitroindazolinones, new prototypes of antichagasic drug

Gómez, María Celeste Vega; Rolón, Míriam; Montero-Torres, Alina; Fonseca-Berzal, Cristina; Escario, José Antonio; Gómez‐Barrio, Alicia; Gálvez, Jorge; Marrero-Ponce, Yovani; Arán, Vicente J.

doi:10.1016/j.ejmech.2012.10.009

Cited by 48 publications

(59 citation statements)

References 52 publications

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“…Concretely, several series of 5-nitroindazole derivatives have achieved important outcomes exhibiting notable anti-T. cruzi activity (Arán et al 2005;Boiani et al 2009;Vega et al 2012;Muro et al 2014), being some of these molecules proposed to trigger reactive oxygen species (ROS)-based mechanisms of action (Folch-Cano et al 2010).…”

Section: Discussionmentioning

confidence: 99%

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

Fonseca‐Berzal

Silva

et al. 2015

Parasitology Open

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In the present study, the potential activity of two 5-nitroindazole derivatives previously proposed as suitable antichagasic prototypes was further evaluated on diverse Trypanosoma cruzi strains 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 (IC 50 = 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 (IC 50 epimastigotes = 3·55 ± 0·47 and 7·92 ± 1·63 µM, IC 50 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.

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Section: Discussionmentioning

confidence: 99%

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

Fonseca‐Berzal

Silva

et al. 2015

Parasitology Open

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“…To further improve this reaction, 4-hydroxyl-L-proline and 1,10-50 phenanthroline were used as ligands respectively for this catalytic system ( Having established the optimal reaction conditions, the scope of this copper catalyzed homo-coupling of N'-aryl benzohydrazides was investigated. Various N'-aryl 5 benzohydrazides with both electron-donating and electronwithdrawing groups attached to the aromatic ring were all good partners in this transformation, affording the corresponding products in good to excellent yields (Table 3). Generally, substrates with electron-donating groups as Me and OMe on Ar 1 10 ring were more effective than these with electron-withdrawing groups on Ar 1 ring (Table 3, entries 7-8, [13][14][16][17].…”

Section: Introductionmentioning

confidence: 99%

Copper(ii)-catalyzed coupling reaction: an efficient and regioselective approach to N′,N′-diaryl acylhydrazines

et al. 2015

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Using N'-aryl acylhydrazines as aryl donors, a novel copper(ii)-catalyzed homo-coupling reaction of N'-aryl acylhydrazines has been developed for the synthesis of N',N'-diaryl acylhydrazines. We also provided a complementary procedure for the preparation of unsymmetrical diaryl acylhydrazines via cross-coupling reaction. These protocols featured mild reaction conditions, wide functional group tolerance and highly regioselective products. Control experiments indicated that this kind of coupling reaction might undergo a transient acyl diazene intermediate.

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Section: Introductionunclassified

“…Es causada por el parásito flagelado Trypanosoma cruzi, cuyo principal vector es un insecto de la clase hemíptera conocido como triatomino. El parási-to también puede ser adquirido por el consumo de alimentos y bebidas contaminadas, trasplantes de órganos, transfusiones sanguíneas y por vía congénita, siendo estas vías menos frecuentes (1,4) .En el curso natural de la enfermedad es posible diferenciar tres fases clínicas: una fase aguda, usualmente asintomá-tica, que tiene lugar de 1 a 3 semanas después de la infección, en donde los pacientes tienen un pronóstico benigno y los síntomas desaparecen después de 1 a 2 meses; una fase indeterminada, en la que no se presentan manifestaciones sintomáticas y, a pesar de que la parasitemia no alcanza los niveles de la fase aguda, el paciente constituye una importante fuente de infección; y la fase crónica, cuya aparición tiene lugar décadas después de las manifestaciones agudas y lleva a condiciones clínicas como cardiomiopatía, arritmias ven- …”

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Tripanosomiasis americana, una mirada desde el tratamiento

et al. 2016

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ResumenLa tripanosomiasis americana o enfermedad de Chagas es una infección parasitaria causada por el parásito flagelado Trypanosoma cruzi, cuyo principal vector es un insecto de la clase hemíptera conocido como triatomino. La quimioterapia, adicional a un control oportuno de vectores y rigurosidad en el control de las transfusiones, son los elementos más importantes para el manejo de esta parasitosis. En la actualidad, el mercado farmacéutico solo ofrece nifurtimox y benznidazol como opciones terapéuticas, y a pesar de que se han obtenido resultados satisfactorios con el uso de estos medicamentos en fases agudas de la enfermedad, tripanosomiasis congénita y accidentes de laboratorio, la efectividad en las fases crónicas es notoriamente menor. Además, ambos fármacos generan ciertos efectos adversos que deben ser tenidos en cuenta por el personal de la salud, antes de iniciar el debido manejo de esta enfermedad. El objetivo del presente artículo es revisar el estado actual del tratamiento farmacológico de la tripanosomiasis americana, buscando resumir los nuevos avances terapéuticos y dar a conocer las limitaciones de los mismos debido a sus efectos adversos. Palabras clave. Enfermedad de Chagas; Tripanosomiasis; Terapéutica. Abstract American trypanosomiasis or Chagas disease is a parasitic infection caused by the flagellate parasite Trypanosoma cruzi, whose main vector is an insect of the Hemiptera class, called triatomine. Chemotherapy, in addition to an appropriate vector control and a rigorous control of transfusions, are the most important strategies for the management of this parasitosis. Currently, the pharmaceutical market only offers nifurtimox and benznidazole as treatment options, and although satisfactory results have been obtained with the use of these drugs in either acute stages of the disease, congenital trypanosomiasis and laboratory accidents, its effectiveness in the chronic phases is significantly smaller. In addition, both drugs produce some side effects that must be taken into account by health workers, before starting the proper management of the disease. The aim of this article is to review the current state of the American trypanosomiasis treatment, in order to summarize the new advances in therapeutics and to introduce their limitations due to adverse effects. Keywords. Chagas Disease; Trypanosomiasis; Therapeutics. An INTRODUCCIÓNLa tripanosomiasis americana, también conocida como enfermedad de Chagas, es la infección parasitaria más importante en las Américas, en donde afecta de 8 a 10 millones de personas (1)(2)(3) . Es causada por el parásito flagelado Trypanosoma cruzi, cuyo principal vector es un insecto de la clase hemíptera conocido como triatomino. El parási-to también puede ser adquirido por el consumo de alimentos y bebidas contaminadas, trasplantes de órganos, transfusiones sanguíneas y por vía congénita, siendo estas vías menos frecuentes (1,4) .En el curso natural de la enfermedad es posible diferenciar tres fases clínicas: una fase aguda, usualmente asintomá-tica, que t...

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Synthesis, biological evaluation and chemometric analysis of indazole derivatives. 1,2-Disubstituted 5-nitroindazolinones, new prototypes of antichagasic drug

Cited by 48 publications

References 52 publications

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

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

Copper(ii)-catalyzed coupling reaction: an efficient and regioselective approach to N′,N′-diaryl acylhydrazines

Tripanosomiasis americana, una mirada desde el tratamiento

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