Histone deacetylases inhibitors as new potential drugs against Leishmania braziliensis, the main causative agent of new world tegumentary leishmaniasis

Souza, Luciana Ângelo de; Bastos, Matheus Silva e; Agripino, Joice de Melo; Onofre, Thiago Souza; Calla, Lourdes Fanny Apaza; Heimburg, Tino; Ghazy, Ehab; Bayer, Theresa; Silva, Victor Hugo Ferraz da; Ribeiro, Paula Dutra; Oliveira, Leandro Licursi de; Bressan, Gustavo Costa; Lamêgo, Márcia Rogéria de Almeida; Silva-Júnior, Abelardo; Vasconcellos, Raphael de Souza; Suarez-Fontes, Ana Márcia; Almeida-Silva, Juliana; Vannier-Santos, Marcos A.; Pierce, Raymond J.; Sippl, Wolfgang; Fietto, Juliana Lopes Rangel

doi:10.1016/j.bcp.2020.114191

Cited by 10 publications

(7 citation statements)

References 80 publications

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“…An antileishmanial assay was carried out as reported by Bastos et al (2017) but with some modifications. Macrophages of the RAW 264.7 strain were kept in a humid oven at 37 • C with 5% CO 2 , with RPMI medium, pH 7.2, supplemented with sodium bicarbonate (2 mg/mL), HEPES (25 mM-pH 7.2) L-glutamine (2 mM), penicillin (0.02 mg/mL), gentamicin (20 µg/mL), and 10% (v/v) fetal bovine serum [42,43].…”

Section: In Vitro Antileishmanial Assaymentioning

confidence: 99%

Annatto Oil Loaded Nanostructured Lipid Carriers: A Potential New Treatment for Cutaneous Leishmaniasis

et al. 2021

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Annatto (Bixa orellana L.) is extensively used as food pigment worldwide. Recently, several studies have found it to have healing and antioxidant properties, as well as effective action against leishmaniasis. Therefore, the purpose of this study was to incorporate the oil obtained from annatto seeds into a nanostructured lipid carrier (NLC) and evaluate its physicochemical properties and biological activity against Leishmania major. Nanoparticles were prepared by the fusion-emulsification and ultrasonication method, with the components Synperonic™ PE (PL) as the surfactant, cetyl palmitate (CP) or myristyl myristate (MM) as solid lipids, annatto oil (AO) (2% and 4%, w/w) as liquid lipid and active ingredient, and ultra-pure water. Physicochemical and biological characterizations were carried out to describe the NLCs, including particle size, polydispersity index (PDI), and zeta potential (ZP) by dynamic light scattering (DLS), encapsulation efficiency (EE%), thermal behavior, X-ray diffraction (XRD), transmission electron microscopy (TEM), Electron Paramagnetic Resonance (EPR), cytotoxicity on BALB/c 3T3 fibroblasts and immortalized human keratinocyte cells, and anti-leishmaniasis activity in vitro. Nanoparticles presented an average diameter of ~200 nm (confirmed by TEM results), a PDI of less than 0.30, ZP between −12.6 and −31.2 mV, and more than 50% of AO encapsulated in NLCs. Thermal analyses demonstrated that the systems were stable at high temperatures with a decrease in crystalline structure due to the presence of AOs (confirmed by XRD). In vitro, the anti-leishmania test displayed good activity in encapsulating AO against L. major. The results indicate that the oily fraction of Bixa orellana L. in NLC systems should be evaluated as a potential therapeutic agent against leishmaniasis.

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Section: In Vitro Antileishmanial Assaymentioning

confidence: 99%

Annatto Oil Loaded Nanostructured Lipid Carriers: A Potential New Treatment for Cutaneous Leishmaniasis

et al. 2021

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“…The compounds act at the gene expression level and deacetylate other proteins that play crucial roles in cell processes such as apoptosis and cell cycle modulation. Through transmission electron microscopy analyses, they found impaired chromatin compaction and the hallmark of cell processes for apoptosis [120]. In a similar study, Di Bello et al tested a variety of compounds from an in-house chemical library as HDAC inhibitors against Leishmania promastigotes.…”

Section: Histone Post-translational Modifications (Hptms)mentioning

confidence: 99%

“…Given the divergence between parasitic HDACs and their orthologs in humans, they are promising therapeutic targets for treating parasite diseases. A case to be highlighted is lysine deacetylases (KDAC), which have high divergence in Leishmania compared with the host, making them an ideal therapeutic target [119,120]. A first approximation was carried out by Loeuillet in 2018, who tested a variety of compounds, including aminophenylhydroxamate, and aminobenzylhydroxamate derivatives.…”

Section: Histone Post-translational Modifications (Hptms)mentioning

confidence: 99%

“…Five compounds had SI and EC 50 values ranging from >3 to 7.6 and 7.21 to 26.5 µM, respectively. TH85 (Figure 8) was the compound with the best activity, with an EC 50 of 7.21 µM, a CC 50 of 54.59 µM, and an SI of 7.6 [120]. Furthermore, the authors determined the mode of action of the HDAC inhibitor compounds.…”

Section: Histone Post-translational Modifications (Hptms)mentioning

confidence: 99%

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Advances in Protozoan Epigenetic Targets and Their Inhibitors for the Development of New Potential Drugs

et al. 2023

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Protozoan parasite diseases cause significant mortality and morbidity worldwide. Factors such as climate change, extreme poverty, migration, and a lack of life opportunities lead to the propagation of diseases classified as tropical or non-endemic. Although there are several drugs to combat parasitic diseases, strains resistant to routinely used drugs have been reported. In addition, many first-line drugs have adverse effects ranging from mild to severe, including potential carcinogenic effects. Therefore, new lead compounds are needed to combat these parasites. Although little has been studied regarding the epigenetic mechanisms in lower eukaryotes, it is believed that epigenetics plays an essential role in vital aspects of the organism, from controlling the life cycle to the expression of genes involved in pathogenicity. Therefore, using epigenetic targets to combat these parasites is foreseen as an area with great potential for development. This review summarizes the main known epigenetic mechanisms and their potential as therapeutics for a group of medically important protozoal parasites. Different epigenetic mechanisms are discussed, highlighting those that can be used for drug repositioning, such as histone post-translational modifications (HPTMs). Exclusive parasite targets are also emphasized, including the base J and DNA 6 mA. These two categories have the greatest potential for developing drugs to treat or eradicate these diseases.

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“…Coding sequences for several of these enzymes have been found in the T. cruzi genome ( El-Sayed et al., 2005 ), and partially characterized ( Moretti et al., 2015 ; Ritagliati et al., 2015 ; Marek et al., 2021 ; Picchi-Constante et al., 2021 ). Inhibitors of KDACs have been found to affect different parasites, including the pathogen causing malaria ( Plasmodium falciparum ), kinetoplastids ( T. cruzi , Trypanosoma brucei and Leishmania donovani ), and nematodes ( Brugiamalayi, Dirofilariaimmitis and Haemonchus contortus ) ( Murray et al., 2001 ; Andrews et al., 2012a , 2012b ; Herrera-Martínez et al., 2020 ; Ghazy et al., 2022 ; Ângelo de Souza et al., 2020 ; Veiga-santos et al., 2014 ; Verçoza et al., 2017 ; de Oliveira Santos et al., 2019 ; Matutino Bastos et al., 2020 ). Moreover, we have recently reported that resveratrol (RSV), previously described as an activator of sirtuin deacetylases ( Andrews et al., 2012b ; Dai et al., 2018 ), reduces the growth of T. cruzi epimastigotes and the infectivity of cell-derived trypomastigotes ( Campo, 2017 ), which agrees with previous reports describing the anti-parasite effects of RSV on Leishmania major ( Kedzierski et al., 2007 ) and other T. cruzi strains ( Valera Vera et al., 2016 ).…”

Section: Introductionmentioning

confidence: 99%

In vitro evaluation of Resveratrol as a potential pre-exposure prophylactic drug against Trypanosoma cruzi infection

Rodríguez¹,

Tekiel²,

Campo³

2022

International Journal for Parasitology: Drugs and Drug Resistan

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Histone deacetylases inhibitors as new potential drugs against Leishmania braziliensis, the main causative agent of new world tegumentary leishmaniasis

Cited by 10 publications

References 80 publications

Annatto Oil Loaded Nanostructured Lipid Carriers: A Potential New Treatment for Cutaneous Leishmaniasis

Annatto Oil Loaded Nanostructured Lipid Carriers: A Potential New Treatment for Cutaneous Leishmaniasis

Advances in Protozoan Epigenetic Targets and Their Inhibitors for the Development of New Potential Drugs

In vitro evaluation of Resveratrol as a potential pre-exposure prophylactic drug against Trypanosoma cruzi infection

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