Synthesis and<i>in vitro</i>Evaluation of New Benzenesulfonamides as Antileishmanial Agents

Borges, Júlio César; Carvalho, Adriana V.; Bernardino, Alice M. R.; Oliveira, César de; Pinheiro, Luiz C. S.; Marra, Roberta K. F.; Castro, Helena C.; Wardell, Solange M. S. V.; Wardell, Jámes L.; Amaral, Verônica F.; Canto‐Cavalheiro, Marilene M.; Leon, Leonor L.; Genestra, Marcelo

doi:10.5935/0103-5053.20140062

Cited by 3 publications

(5 citation statements)

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“…As shown in Fig. 1 , the 4-chloroquinolines were quickly prepared from 4-oxo-1,4-dihydroquinolines-3-carbonitriles using a methodology described by Gould-Jacobs and co-workers ( Borges et al., 2014 ).…”

Section: Resultsmentioning

confidence: 99%

“…Preparation of the 4-arylaminoquinoline-3-carbonitrile derivatives: 1.0 mmol of 4-chloroquinolines (2) and 1.5 mmol of corresponding aniline were stirred in 6.0 mL of diethyleneglycol at 120 °C for 1 h. Finally, the mixture was placed in a beaker of ice and water. The crystals formed were filtered and recrystalized in ethanol ( Borges et al., 2014 , Leal et al., 2008 ). Subsequently, all compounds formed (1 a –1 g ) were identified by 1 H NMR, 13 C NMR and FT-IR spectroscopies ( Supplementary Material ).…”

Section: Methodsmentioning

confidence: 99%

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Interactions between 4-aminoquinoline and heme: Promising mechanism against Trypanosoma cruzi

Lechuga

Borges

Calvet

et al. 2016

International Journal for Parasitology: Drugs and Drug Resistan

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Chagas disease is a neglected tropical disease caused by the flagellated protozoan Trypanosoma cruzi. The current drugs used to treat this disease have limited efficacy and produce severe side effects. Quinolines, nitrogen heterocycle compounds that form complexes with heme, have a broad spectrum of antiprotozoal activity and are a promising class of new compounds for Chagas disease chemotherapy. In this study, we evaluated the activity of a series of 4-arylaminoquinoline-3-carbonitrile derivatives against all forms of Trypanosoma cruzi in vitro. Compound 1g showed promising activity against epimastigote forms when combined with hemin (IC50<1 μM), with better performance than benznidazole, the reference drug. This compound also inhibited the viability of trypomastigotes and intracellular amastigotes. The potency of 1g in combination with heme was enhanced against epimastigotes and trypomastigotes, suggesting a similar mechanism of action that occurs in Plasmodium spp. The addition of hemin to the culture medium increased trypanocidal activity of analog 1g without changing the cytotoxicity of the host cell, reaching an IC50 of 11.7 μM for trypomastigotes. The mechanism of action was demonstrated by the interaction of compound 1g with hemin in solution and prevention of heme peroxidation. Compound 1g and heme treatment induced alterations of the mitochondrion-kinetoplast complex in epimastigotes and trypomastigotes and also, accumulation of electron-dense deposits in amastigotes as visualized by transmission electron microscopy. The trypanocidal activity of 4-aminoquinolines and the elucidation of the mechanism involving interaction with heme is a neglected field of research, given the parasite's lack of heme biosynthetic pathway and the importance of this cofactor for parasite survival and growth. The results of this study can improve and guide rational drug development and combination treatment strategies.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Interactions between 4-aminoquinoline and heme: Promising mechanism against Trypanosoma cruzi

Lechuga

Borges

Calvet

et al. 2016

International Journal for Parasitology: Drugs and Drug Resistan

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“…It was reported earlier that a number of sulfonyl or sulphonamide functional group containing heterocyclic compounds were utilised to demonstrate potential anti-inflammatory activity [99e103]. Moreover, among the highly marketed COX-2 inhibitors that comprise the sulphonamide moiety, SC-558 (165) and celecoxib (166) ( Fig. 11) are the major determinant for COX-2 selectivity and in vivo efficacy.…”

Section: Anti-inflammatory Activitymentioning

confidence: 99%

“…Among these, compound 232 (IC 50 value is 6.7 mM) ( Fig. 27) was found to have the most potent activity against Leishmania amazonensis with IC 50 value higher than reference drug ketoconazole [165]. Gonz alez-Rosende et al developed a new series of naphthalene-sulfonamide analogues as potent antileishmanial and trypanocidal inhibitors.…”

Section: Antileishmanial Activitymentioning

confidence: 99%

Pharmaceutical and medicinal significance of sulfur (SVI)-Containing motifs for drug discovery: A critical review

Zhao

Rakesh

Ravidar

et al. 2019

European Journal of Medicinal Chemistry

376

169

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a b s t r a c tSulfur (S VI ) based moieties, especially, the sulfonyl or sulfonamide based analogues have showed a variety of pharmacological properties, and its derivatives propose a high degree of structural diversity that has established useful for the finding of new therapeutic agents. The developments of new less toxic, low cost and highly active sulfonamides containing analogues are hot research topics in medicinal chemistry. Currently, more than 150 FDA approved Sulfur (S VI )-based drugs are available in the market, and they are widely used to treat various types of diseases with therapeutic power. This comprehensive review highlights the recent developments of sulfonyl or sulfonamides based compounds in huge range of therapeutic applications such as antimicrobial, anti-inflammatory, antiviral, anticonvulsant, antitubercular, antidiabetic, antileishmanial, carbonic anhydrase, antimalarial, anticancer and other medicinal agents. We believe that, this review article is useful to inspire new ideas for structural design and developments of less toxic and powerful Sulfur (S VI ) based drugs against the numerous death-causing diseases.

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“…Of note, several pyrazole-based series of antileishmanial compounds have been reported by research groups in Brazil, but these generally have modest–weak activity against Leishmania species (e.g., L. amazonensis) that cause cutaneous leishmaniasis (CL), not VL. ,,− Consequently, there is an urgent need for additional research into more effective therapeutic options for the treatment of VL. − …”

Section: Introductionmentioning

confidence: 99%

Novel Amino-pyrazole Ureas with Potent In Vitro and In Vivo Antileishmanial Activity

et al. 2015

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Visceral leishmaniasis is a severe parasitic disease that is one of the most neglected tropical diseases. Treatment options are limited, and there is an urgent need for new therapeutic agents. Following an HTS campaign and hit optimization, a novel series of amino-pyrazole ureas has been identified with potent in vitro antileishmanial activity. Furthermore, compound 26 shows high levels of in vivo efficacy (>90%) against Leishmania infantum, thus demonstrating proof of concept for this series.

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Synthesis andin vitroEvaluation of New Benzenesulfonamides as Antileishmanial Agents

Cited by 3 publications

References 1 publication

Interactions between 4-aminoquinoline and heme: Promising mechanism against Trypanosoma cruzi

Interactions between 4-aminoquinoline and heme: Promising mechanism against Trypanosoma cruzi

Pharmaceutical and medicinal significance of sulfur (SVI)-Containing motifs for drug discovery: A critical review

Novel Amino-pyrazole Ureas with Potent In Vitro and In Vivo Antileishmanial Activity

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