<i>Leishmania infantum</i> arginase: biochemical characterization and inhibition by naturally occurring phenolic substances

Garcia, Andreza R.; Oliveira, Danielle Maria Perpétua de; Amaral, Ana Cláudia F.; Jesus, Jéssica Barbosa de; Sodero, Ana Carolina Rennó; Souza, Alessandra Mendonça Teles de; Supuran, Claudiu T.; Vermelho, Alane Beatriz; Rodrigues, Igor A.; Pinheiro, Anderson S.

doi:10.1080/14756366.2019.1616182

Cited by 39 publications

(45 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Both compounds have previously been identified in P. guajava and suggested to be good candidates for the development of new treatments for sickle cell anemia [33]. Furthermore, we have demonstrated their role in ROS scavenging activity, with antioxidant capacity comparable to rosmarinic acid and caffeic acid [34]. Corosolic acid has been shown to prevent inflammation and hypertension in rats [35] and to reduce the plasma glucose level in humans [19].…”

Section: Discussionmentioning

confidence: 60%

Antileishmanial Compounds Isolated from Psidium Guajava L. Using a Metabolomic Approach

et al. 2019

View full text Add to dashboard Cite

With an estimated annual incidence of one million cases, leishmaniasis is one of the top five vector-borne diseases. Currently available medical treatments involve side effects, including toxicity, non-specific targeting, and resistance development. Thus, new antileishmanial chemical entities are of the utmost interest to fight against this disease. The aim of this study was to obtain potential antileishmanial natural products from Psidium guajava leaves using a metabolomic workflow. Several crude extracts from P. guajava leaves harvested from different locations in the Lao People's Democratic Republic (Lao PDR) were profiled by liquid chromatography coupled to high-resolution mass spectrometry, and subsequently evaluated for their antileishmanial activities. The putative active compounds were highlighted by multivariate correlation analysis between the antileishmanial response and chromatographic profiles of P. guajava mixtures. The results showed that the pooled apolar fractions from P. guajava were the most active (IC 50 = 1.96 ± 0.47 µg/mL). Multivariate data analysis of the apolar fractions highlighted a family of triterpenoid compounds, including jacoumaric acid (IC 50 = 1.318 ± 0.59 µg/mL) and corosolic acid (IC 50 = 1.01 ± 0.06 µg/mL). Our approach allowed the identification of antileishmanial compounds from the crude extracts in only a small number of steps and can be easily adapted for use in the discovery workflows of several other natural products.Molecules 2019, 24, 4536 2 of 13 of the human population to the parasite, and human behavior [3]. The disease is characterized by four forms; visceral leishmaniasis, post-kala-azar dermal leishmaniasis, cutaneous leishmaniasis, and mucocutaneous leishmaniasis [4]. Available medical treatments are not sufficient because of their extensive toxicity (e.g., the nephrotoxicity of amphotericin B, the teratogenicity of miltefosine), their lack of efficacy, their expensive cost (amphotericin B), the development of drug resistance (sodium stibogluconate and meglumine antimoniate), and non-specific targeting [4,5]. Fexinidazole, a 5-nitroimidazole, was recently in phase II of clinical trials on visceral leishmaniasis but exhibited a lack of efficacy, and in 2018 no new lead molecules were included in clinical trials [4].Control of leishmaniasis by traditional approaches (vector control and treatment of patients) is facing the difficulties of identifying new cost-effectively produced bioactive molecules able to be produced on an industrial scale, rapid development of drug resistance, and the lack of access to drugs by the threatened populations. These issues are at the heart of concerns of the WHO regarding the control of tropical diseases [6]. Therefore, combination therapies are used to improve the efficacy of antileishmanial therapies and can shorten treatment duration [7]. Furthering our fundamental knowledge through original approaches, herein concerning the activity of natural compounds from a promising plant species active against Leishmania spp., is vital to ov...

show abstract

Section: Discussionmentioning

confidence: 60%

Antileishmanial Compounds Isolated from Psidium Guajava L. Using a Metabolomic Approach

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Murine Macrophage (MØs) like tumor cell, RAW 264.7 was obtained from American Type Culture Collection and maintained in complete RPMI 1640 medium supplemented with 10% FBS at 37°C and 5% CO 2 atmosphere. For cytotoxic evaluation, Raw 264.7 macrophages (at a density of 10 5 cells/well) were plated in 96-well cell culture plates and incubated with different concentrations of suramin (1–400 μM) for 48hrs [ 14 ]. Cell viability was determined by the MTT assay and the 50% cytotoxic concentration (CC 50 ) was calculated as stated earlier [ 8 ].…”

Section: Methodsmentioning

confidence: 99%

In vivo experiments demonstrate the potent antileishmanial efficacy of repurposed suramin in visceral leishmaniasis

et al. 2020

View full text Add to dashboard Cite

Background Treatment failure and resistance to the commonly used drugs remains a major obstacle for successful chemotherapy against visceral leishmaniasis (VL). Since the development of novel therapeutics involves exorbitant costs, the effectiveness of the currently available antitrypanosomatid drug suramin has been investigated as an antileishmanial, specifically for VL,in vitro and in animal model experiments. Methodology/Principal Leishmania donovani promastigotes were treated with suramin and studies were performed to determine the extent and mode of cell mortality, cell cycle arrest and other in vitro parameters. In addition, L. donovani infected BALB/c mice were administered suramin and a host of immunological parameters determined to estimate the antileishmanial potency of the drug. Finally, isothermal titration calorimetry (ITC) and enzymatic assays were used to probe the interaction of the drug with one of its putative targets namely parasitic phosphoglycerate kinase (LmPGK). Findings The in vitro studies revealed the potential efficacy of suramin against the Leishmania parasite. This observation was further substantiated in the in vivo murine model, which demonstrated that upon suramin administration, the Leishmania infected BALB/c mice were able to reduce the parasitic burden and also generate the host protective immunological responses. ITC and enzyme assays confirmed the binding and consequent inhibition of LmPGK due to the drug.

show abstract

“…After the in silico evaluation, bioguide assays were developed. Caffeic acid showed IC 50 values of 12.5 µg/mL against promastigotes (Bortoleti et al, 2019), 16.0 µM against intracellular amastigotes of Leishmania amazonensis (Montrieux et al, 2014) and 21.9 µM for intracellular amastigotes of L. infantum (Garcia et al, 2019) (Table 4). Regarding these promising in vitro results, the effects of caffeic acid in an in vivo model of infection were examined.…”

Section: Caffeic Acidmentioning

confidence: 99%

Use of Natural Products in Leishmaniasis Chemotherapy: An Overview

et al. 2020

View full text Add to dashboard Cite

Leishmaniasis is an infectious parasitic disease that is caused by protozoa of the genus Leishmania, a member of the Trypanosomatidae family. Leishmaniasis is classified by the World Health Organization as a neglected tropical disease that is responsible for millions of deaths worldwide. Although there are many possible treatments for leishmaniasis, these treatments remain mostly ineffective, expensive, and long treatment, as well as causing side effects and leading to the development of resistance. For novel and effective treatments to combat leishmaniasis, many research groups have sought to utilize natural products. In addition to exhibiting potential as therapeutic compounds, natural products may also contribute to the development of new drugs based on their chemical structures. This review presents the most promising natural products, including crude extracts and isolated compounds, employed against Leishmania spp.

show abstract

Leishmania infantum arginase: biochemical characterization and inhibition by naturally occurring phenolic substances

Cited by 39 publications

References 81 publications

Antileishmanial Compounds Isolated from Psidium Guajava L. Using a Metabolomic Approach

Antileishmanial Compounds Isolated from Psidium Guajava L. Using a Metabolomic Approach

In vivo experiments demonstrate the potent antileishmanial efficacy of repurposed suramin in visceral leishmaniasis

Use of Natural Products in Leishmaniasis Chemotherapy: An Overview

Contact Info

Product

Resources

About