Synthesis and biological properties of new 5-nitroindazole derivatives

Arán, Vicente J.; Ochoa, Carmen; Boiani, Lucı́a; Buccino, Pablo; Cerecetto, Hugo; Gerpe, Alejandra; González, Mercedes; Montero, David; Nogal, Juan José; Gómez‐Barrio, Alicia; Azqueta, Amaya; Ceráin, Adela López de; Piro, Oscar E.; Castellano, Eduardo E.

doi:10.1016/j.bmc.2005.02.043

Cited by 67 publications

(40 citation statements)

References 19 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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“…The selectivity indexes, SI, were expressed as the ratio between IC 50 in macrophages and IC 50 in T. cruzi (Tulahuen 2 strain). [58,59] …”

Section: Cytotoxicity In Mammalian Cellsmentioning

confidence: 99%

Novel quinoxaline 1,4-di-N-oxide derivatives as new potential antichagasic agents

Torres

Moreno‐Viguri

Galiano

et al. 2013

European Journal of Medicinal Chemistry

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ABSTRACT. As a continuation of our research and with the aim of obtaining new agents against Chagas disease, an extremely neglected disease which threatens 100 million people, eighteen new quinoxaline 1,4-di-N-oxide derivatives have been synthesized following the Beirut reaction. The synthesis of the new derivatives was optimized through the use of a new and more efficient microwave-assisted organic synthetic method. The new derivatives showed excellent in vitro biological activity against Trypanosoma cruzi. Compound 17, which was substituted with 2 fluoro groups at the 6-and 7-positions of the quinoxaline ring, was the most active and selective in the cytotoxicity assay. The electrochemical study showed that the most active compounds, which were substituted by electron-withdrawing groups, possessed a greater ease of reduction of the N-oxide groups.

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“…In recent years, we have developed different methods of the synthesis of indazoles, [1][2][3][4] indoles, [5] cinnolines [6] and quinoxalines.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Evaluation of 1,1′‐Hydrocarbylenebis(indazol‐3‐ols) as Potential Antimalarial Drugs

et al. 2009

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Bis(indazol-3-ol) derivatives (5, 30-38) were prepared by alkylation of 3-alkoxyindazoles with alpha,omega-dibromides, followed by removal of the O-protecting groups. These compounds were subsequently evaluated as inhibitors of biocrystallization of ferriprotoporphyrin IX (heme) to hemozoin, a Plasmodium detoxification specific process. Most bis(5-nitroindazol-3-ols) were good inhibitors, however, a denitro analogue (38), the intermediate bis(3-alkoxyindazoles) (15-29) as well as bis(indazolin-3-ones) (39-42) were not active, showing the importance of the NO(2) and OH groups in the inhibition process.

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Synthesis and biological properties of new 5-nitroindazole derivatives

Cited by 67 publications

References 19 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

Novel quinoxaline 1,4-di-N-oxide derivatives as new potential antichagasic agents

Synthesis and Evaluation of 1,1′‐Hydrocarbylenebis(indazol‐3‐ols) as Potential Antimalarial Drugs

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