Aminoquinoline compounds: Effect of 7-chloro-4-quinolinylhydrazone derivatives against Leishmania amazonensis

Antinarelli, Luciana Maria Ribeiro; Souza, Isabela de Oliveira; Glanzmann, Nícolas; Almeida, Ayla das Chagas; Porcino, Gabriane Nascimento; Vasconcelos, Eveline Gomes; Silva, Adilson David da; Coimbra, Elaine Soares

doi:10.1016/j.exppara.2016.10.009

Cited by 24 publications

(24 citation statements)

References 36 publications

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“…Peritoneal macrophages used in this study were obtained according to previous report. [41] The values of cytotoxicity concentration to reduce 50 % of viable macrophages (CC 50 ) were obtained using GraFit Version 5 software.…”

Section: Cytotoxicity Assaymentioning

confidence: 99%

In Vitro and in Vivo Antischistosomal Activities of Chalcones

Pereira

Alves

Silveira

et al. 2018

Chemistry & Biodiversity

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In this study, we evaluated the in vitro and in vivo schistosomicidal activities of chalcones against Schistosoma mansoni worms. In vitro assays revealed that chalcones 1 and 3 were the most active compounds, without affecting significantly mammalian cells. Confocal laser scanning microscopy and scanning electron microscopy studies revealed reduction on the numbers of tubercles and morphological alterations in the tegument of S. mansoni worms after in vitro incubation with chalcones 1 and 3. In a mouse model of schistosomiasis, the oral treatment (400 mg/kg) with chalcone 1 or 3 significantly caused a total worm burden reduction in mice. Chalcone 1 showed significant inhibition of the S. mansoni ATP diphosphohydrolase activity, which was corroborated by molecular docking studies. The results suggested that chalcones could be explored as lead compounds with antischistosomal properties.

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Section: Cytotoxicity Assaymentioning

confidence: 99%

In Vitro and in Vivo Antischistosomal Activities of Chalcones

Pereira

Alves

Silveira

et al. 2018

Chemistry & Biodiversity

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“…ROS generation was fluorimetrically quantified at an excitation wavelength of 485 nm and an emission wavelength of 528 nm. Promastigotes incubated with miltefosine (42.0 μ m ) were used as a positive control …”

Section: Methodsmentioning

confidence: 99%

“…Subsequently, the parasites were washed twice with PBS, and data acquisition was performed using a fluorimeter (FLx800), at excitation and emission wavelengths of 540 and 600 nm, respectively. Promastigotes incubated with 20.0 μ m carbonyl cyanide‐4‐(trifluoromethoxy)phenylhydrazone (FCCP, Sigma–Aldrich) were used as positive control …”

Section: Methodsmentioning

confidence: 99%

“…Promastigotes incubated with miltefosine (42.0 mm)w ere used as apositive control. [14] Determination of DY m : L. amazonensis promastigote forms (1 10 7 cells mL À1 )w ere untreated or treated with 17.28 or 34.56 mm compound 2u at 25 8CinaBOD incubator.After 24 h, the parasites were washed with PBS and incubated with 500 nm MitoTracker Red (Life Te chnologies, CA, USA) for 40 min at 25 8Ci nt he dark in aB OD incubator.S ubsequently,t he parasites were washed twice with PBS, and data acquisition was performed using af luorimeter (FLx800), at excitation and emission wavelengths of 540 and 600 nm, respectively.P romastigotes incubated with 20.0 mm carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone (FCCP,S igma-Aldrich) were used as positive control. [14] Statistical analysis:D ata were analyzed using one-way ANOVA, and significant differences among means were identified using Dunnett'st est.…”

Section: Methodsmentioning

confidence: 99%

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Synthesis, Biological Activity, and Mechanism of Action of 2‐Pyrazyl and Pyridylhydrazone Derivatives, New Classes of Antileishmanial Agents

et al. 2018

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In this work, we report the antileishmanial activity of 23 compounds based on 2-pyrazyl and 2-pyridylhydrazone derivatives. The compounds were tested against the promastigotes of Leishmania amazonensis and L. braziliensis, murine macrophages, and intracellular L. amazonensis amastigotes. The most potent antileishmanial compound was selected for investigation into its mechanism of action. Among the evaluated compounds, five derivatives [(E)-3-((2-(pyridin-2-yl)hydrazono)methyl)benzene-1,2-diol (2 b), (E)-4-((2-(pyridin-2-yl)hydrazono)methyl)benzene-1,3-diol (2 c), (E)-4-nitro-2-((2-(pyrazin-2-yl)hydrazono)methyl)phenol (2 s), (E)-2-(2-(pyridin-2-ylmethylene)hydrazinyl)pyrazine (2 u), and (E)-2-(2-((5-nitrofuran-2-yl)methylene)hydrazinyl)pyrazine (2 v)] exhibited significant activity against L. amazonensis amastigote forms, with IC values below 20 μm. The majority of the compounds did not show any toxic effect on murine macrophages. Preliminary studies on the mode of action of members of this hydrazine-derived series indicate that the accumulation of reactive oxygen species (ROS) and disruption of parasite mitochondrial function are important for the pharmacological effect on L. amazonensis promastigotes.

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“…However, these drugs are of high cost, require long‐term therapy or are highly toxic, and, in general, they are administered by an intravenous or intramuscular route in different protocols that require hospital internment . Therefore, new compounds and strategies against leishmaniasis are being developed …”

Section: Introductionmentioning

confidence: 99%

The alkylaminoalkanethiosulfuric acids exhibit in-vitro antileishmanial activity against Leishmania (Viannia) braziliensis: a new perspective for use of these schistosomicidal agents

Porcino

Antinarelli

Maia

et al. 2019

Journal of Pharmacy and Pharmacology

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The alkylaminoalkanethiosulfuric acids (AAATs) are amphipathic compounds effective against experimental schistosomiasis, of low toxicity, elevated bioavailability after a single oral dose and prompt tissue absorption.Objectives To explore the in-vitro antileishmanial potential of AAATs using five compounds of this series against Leishmania (Viannia) braziliensis. Methods Their effects on promastigotes and axenic amastigotes, and cytotoxicity to macrophages were tested by the MTT method, and on Leishmania-infected macrophages by Giemsa stain. Effects on the mitochondrial membrane potential of promastigotes and axenic amastigotes and DNA of intracellular amastigotes were tested using JC-1 and TUNEL assays, respectively. Key findings The 2-(isopropylamino)-1-octanethiosulfuric acid (I) and 2-(secbutylamino)-1-octanethiosulfuric acid (II) exhibit activity against both promastigotes and intracellular amastigotes (IC 50 25-35 µm), being more toxic to intracellular parasites than to the host cell. Compound I induced a loss of viability of axenic amastigotes, significantly reduced (30%) the mitochondrial membrane potential of both promastigotes and axenic amastigotes and promoted selective DNA fragmentation of the nucleus and kinetoplast of intracellular amastigotes.Conclusions In this previously unpublished study of trypanosomatids, it is shown that AAATs could also exhibit selective antileishmanial activity, a new possibility to be investigated in oral treatment of leishmaniasis.

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Aminoquinoline compounds: Effect of 7-chloro-4-quinolinylhydrazone derivatives against Leishmania amazonensis

Cited by 24 publications

References 36 publications

In Vitro and in Vivo Antischistosomal Activities of Chalcones

In Vitro and in Vivo Antischistosomal Activities of Chalcones

Synthesis, Biological Activity, and Mechanism of Action of 2‐Pyrazyl and Pyridylhydrazone Derivatives, New Classes of Antileishmanial Agents

The alkylaminoalkanethiosulfuric acids exhibit in-vitro antileishmanial activity against Leishmania (Viannia) braziliensis: a new perspective for use of these schistosomicidal agents

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