Leishmaniasis and Chagas Disease – Neglected Tropical Diseases: Treatment Updates

Sangenito, Leandro S.; Santos, Vanessa da Silva; d’Avila-Levy, Claudia M.; Branquinha, Marta H.; Santos, André Luis Souza dos; Oliveira, Simone S. C.

doi:10.2174/156802661903190328155136

Cited by 43 publications

(34 citation statements)

References 16 publications

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“…This disease is characterised by a spectrum of clinical manifestations ranging from cutaneous ulcers to deadly visceral lesions. The present therapy for leishmaniasis is limited to few drugs that are associated with disadvantages such as unacceptable toxicity, difficulties during administration, and treatment failure 1 2 …”

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confidence: 99%

“…L . braziliensis is associated with mucosal and disseminated leishmaniasis to a greater extent than other New World Leishmania , and is the most widely distributed causative agent of cutaneous leishmaniasis in Brazil 1 2 Therefore, owing to the severity and public health importance of L. braziliensis , the Drugs for Neglected Diseases initiative (DND i ) decided to focus on the development of novel treatment options for cutaneous leishmaniasis, predominantly caused by this species 15 .…”

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confidence: 99%

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Calpains of Leishmania braziliensis: genome analysis, differential expression, and functional analysis

Ennes-Vidal

Vitório

Menna-Barreto

et al. 2019

Mem. Inst. Oswaldo Cruz

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BACKGROUND Calpains are proteins belonging to the multi-gene family of calcium-dependent cysteine peptidases that undergo tight on/off regulation, and uncontrolled proteolysis of calpains is associated with severe human pathologies. Calpain orthologues are expanded and diversified in the trypanosomatids genome.OBJECTIVES Here, we characterised calpains in Leishmania braziliensis, the main causative agent of cutaneous leishmaniasis in Brazil.METHODS/FINDINGS In total, 34 predicted calpain-like genes were identified. After domain structure evaluation, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) during in vitro metacyclogenesis revealed (i) five genes with enhanced expression in the procyclic stage, (ii) one augmented gene in the metacyclic stage, and (iii) one procyclic-exclusive transcript. Western blot analysis revealed that an antibody against a consensus-conserved peptide reacted with multiple calpain-like proteins, which is consistent with the multi-gene family characteristic. Flow cytometry and immunocytochemistry analyses revealed the presence of calpain-like molecules mainly in the cytoplasm, to a lesser extent in the plasma membrane, and negligible levels in the nucleus, which are all consistent with calpain localisation. Eventually, the calpain inhibitor MDL28170 was used for functional studies revealing (i) a leishmaniostatic effect, (ii) a reduction in the association index in mouse macrophages, (iii) ultra-structural alterations conceivable with autophagy, and (iv) an enhanced expression of the virulence factor GP63.CONCLUSION This report adds novel insights into the domain structure, expression, and localisation of L. braziliensis calpain-like molecules.

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confidence: 99%

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confidence: 99%

Calpains of Leishmania braziliensis: genome analysis, differential expression, and functional analysis

Ennes-Vidal

Vitório

Menna-Barreto

et al. 2019

Mem. Inst. Oswaldo Cruz

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“…Medicinal plants are usually used in folk medicine to treat parasitic diseases. Several studies corroborate the therapeutic importance of natural products in American trypanosomiasis [10,11]. Substances of several classes, such as quinones, flavonoids, alkaloids, and terpenes, have anti-T. cruzi activity and have the potential to be new drugs for Chagas' disease treatment [12].…”

Section: Introductionmentioning

confidence: 86%

Anti-Trypanosoma cruzi activity, cytotoxicity and, chemical characterization of extracts from seeds of Lonchocarpus cultratus

Griebler

Banhuk

Staffen

et al. 2021

J Infect Dev Ctries

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Introduction: Trypanosoma cruzi is the agent of Chagas’ disease and affects approximately 6-8 million people worldwide. The search for new anti-T. cruzi drugs are relevant because only two drugs exist actually. The objective of this study was to investigate the effect of the extracts from the seeds of Lonchocarpus cultratus on T. cruzi, its cytotoxicity as well as to elucidate its chemical profile. Methodology: The characterization of the extracts was done using 1H-RMN. T. cruzi forms were treated with increasing concentrations of the extracts and after, the percentage of inhibition and IC50 or LC50 were calculated. Murine peritoneal macrophages were treated with different concentrations of the extracts to evaluate the cellular viability. The hemotoxicity was accessed by verifying the levels of hemolysis caused by the extracts on human red blood cells. Results: Chalcones isocordoin and lonchocarpin were detected in the dichloromethane extract, and chalcone lonchocarpin was detected in the hexane extract. The dichloromethane extract showed higher activity against all the forms of T. cruzi compared to the other two extracts, but the hexane showed the best selectivity index. The cytotoxicity observed in murine macrophages was confirmed in human erythrocytes, with dichloromethane extract having the highest toxicity. The methanolic extract showed the lowest anti-T. cruzi activity but was nontoxic to peritoneal murine macrophages and red blood cells. Conclusions: L. cultratus extracts have the potential to be explored for the development of new anti-trypanosomal drugs. This study was the first to demonstrate the action of extracts from the genus Lonchocarpus on infecting forms of T. cruzi.

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“…and Trypanosoma brucei sensu lato, respectively [2]. These parasites affect about 22 million people worldwide and alternate their life cycle between an insect vector and a mammalian host [3]. Therefore, the research is concentrated in these disease-inflicting parasites, however, the largest biodiversity of this family is among trypanosomatids that usually infects insects as the single host [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

First Draft Genome of the Trypanosomatid Herpetomonas muscarum ingenoplastis through MinION Oxford Nanopore Technology and Illumina Sequencing

et al. 2020

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Leishmaniasis and Chagas Disease – Neglected Tropical Diseases: Treatment Updates

Cited by 43 publications

References 16 publications

Calpains of Leishmania braziliensis: genome analysis, differential expression, and functional analysis

Calpains of Leishmania braziliensis: genome analysis, differential expression, and functional analysis

Anti-Trypanosoma cruzi activity, cytotoxicity and, chemical characterization of extracts from seeds of Lonchocarpus cultratus

First Draft Genome of the Trypanosomatid Herpetomonas muscarum ingenoplastis through MinION Oxford Nanopore Technology and Illumina Sequencing

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