Amino Acid and Polyamine Membrane Transporters in Trypanosoma cruzi: Biological Function and Evaluation as Drug Targets

Sayé, Melisa; Reigada, Chantal; Gauna, Lucrecia; Valera-Vera, Edward; Pereira, Claudio A.; Miranda, Mariana R.

doi:10.2174/0929867326666190620094710

Cited by 5 publications

(3 citation statements)

References 99 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The selective inhibition of transporters has been proposed as a valuable target to develop new medications against different pathologies including neurological disorders (Qosa et al, 2016 ) and parasitic diseases (Sayé et al, 2019 ). The specific inhibition of neuronal glycine, alanine, serine, and cysteine transporters have been studied as molecular targets for new treatment of schizophrenia (Pinard et al, 2010 ; Schneider et al, 2012 ; Carland et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Targeting L-Proline Uptake as New Strategy for Anti-chagas Drug Development

et al. 2020

View full text Add to dashboard Cite

L-Proline is an important amino acid for the pathogenic protists belonging to Trypanosoma and Leishmania genera. In Trypanosoma cruzi, the etiological agent of Chagas disease, this amino acid is involved in fundamental biological processes such as ATP production, differentiation of the insect and intracellular stages, the host cell infection and the resistance to a variety of stresses. In this study, we explore the L-Proline uptake as a chemotherapeutic target for T. cruzi. Novel inhibitors have been proposed containing the amino acid with a linker and a variable region able to block the transporter. A series of sixteen 1,2,3-triazolyl-proline derivatives have been prepared for in vitro screening against T. cruzi epimastigotes and proline uptake assays. We successfully obtained inhibitors that interfere with the amino acid internalization, which validated our design targeting the metabolite's transport. The presented structures are one of few examples of amino acid transporter inhibitors. The unprecedent application of this strategy on the development of new chemotherapy against Chagas disease, opens a new horizon on antiparasitic drug development against parasitic diseases and other pathologies.

show abstract

Section: Discussionmentioning

confidence: 99%

Targeting L-Proline Uptake as New Strategy for Anti-chagas Drug Development

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Amines play an important role in a range of metabolic processes in living organisms ( Vissers et al, 2005 ; Pegg, 2009 ; Huang et al, 2011 ; Bröer and Bröer, 2017 ; Greene et al, 2019 ; Sayé et al, 2019 ), such as transcription and translation of genes, structural regulation of chromatin and proteins, cell growth and migration, as well as in the synthesis and metabolism of nucleic acids ( Tremblay, 2007 ; Wallace, 2009 ; Doeun et al, 2017 ; Zhang et al, 2021 ). Dysregulation of these metabolites may lead to various diseases, indicating the potential application of amines in the prediction of disease processes, and prognosis assessment ( Soga et al, 2011 ; Zembron-Lacny et al, 2021 ; Wu et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Profiling of amines in biological samples using polythioester-functionalized magnetic nanoprobe

Qiu

Zhang

Lai

et al. 2023

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

Introduction: The metabolic balance of amines is closely related to human health. It remains a great challenge to analyze amines with high-throughput and high-coverage.Methods: Polythioester-functionalized magnetic nanoprobes (PMPs) have been prepared under mild conditions and applied in chemoselective capture of amides. With the introduction of polythioester, PMPs demonstrate remarkably increased capture efficiency, leading to the dramatically improved sensitivity of mass spectrometry detection.Results: The analysis method with PMPs treatment has been applied in rapid detection of more than 100 amines in lung adenocarcinoma cell lines, mouse organ tissues, and 103 human serum samples with high-throughput and high-coverage. Statistical analysis shows that arginine biosynthesis differed between lung adenocarcinoma cell lines.Discussion: Phenylalanine, tyrosine and tryptophan biosynthesis differed between tissues. The combination indicators demonstrate a great diagnostic accuracy for distinguishing between health and lung disease subjects as well as differentiating the patients with benign lung disease and lung cancer. With powerful capture ability, low-cost preparation, and convenient separation, the PMPs demonstrate promising application in the intensive study of metabolic pathways and early diagnosis of disease.high-throughput and high-coverage. Here, polythioester-functionalized magnetic nanoprobes (PMPs) have been prepared under mild conditions and applied in chemoselective capture of amides. With the introduction of polythioester, PMPs demonstrate remarkably increased capture efficiency, leading to the dramatically improved sensitivity of mass spectrometry detection. The analysis method with PMPs treatment has been applied in rapid detection of more than 100 amines in lung adenocarcinoma cell lines, mouse organ tissues, and 103 human serum samples with high-throughput and high-coverage. Statistical analysis shows that arginine biosynthesis differed between lung adenocarcinoma cell lines. Phenylalanine, tyrosine and tryptophan biosynthesis differed between tissues. The combination indicators demonstrate a great diagnostic accuracy for distinguishing between health and lung disease subjects as well as differentiating the patients with benign lung disease and lung cancer. With powerful capture ability, low-cost preparation, and convenient separation, the PMPs demonstrate promising application in the intensive study of metabolic pathways and early diagnosis of disease.

show abstract

“…Sayé et al [7] propose the most represented family of amino acid and derivative transporters in T. cruzi as drug targets, focalizing in proline and polyamine permeases. This family is absent in the human host and their members are responsible of the acquisition of relevant nutrients for the survival of the parasite.…”

mentioning

confidence: 99%

Chagas Disease Treatment: From New Therapeutic Targets to Drug Discovery and Repositioning

Miranda

Sayé

2019

CMC

Self Cite

View full text Add to dashboard Cite

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, currently affects millions of people worldwide although it is only endemic in America. Chagas is considered a neglected tropical disease because it afflicts the low-income and poorest populations in developing regions of the Americas, particularly in remote, rural areas where infrastructure such as adequate housing, sanitation and clinical resources are limited. In addition, governments pay scarce or no attention to this health problem. Benznidazole and nifurtimox, both discovered more than 50 years ago, are the only two drugs available to treat Chagas disease and not only present severe side effects but also are ineffective in the chronic phase of the disease when most of the patients are diagnosed. Recent efforts to develop new treatments for Chagas disease, including posaconazole repositioning and the prodrug of ravuconazole (E1224) trial, have been unsuccessful and remark the urgent need to develop new therapeutic alternatives. The scientific effort must be focused in finding simple, safe and effective drugs that directly target the parasite without harming the patients.

show abstract

Amino Acid and Polyamine Membrane Transporters in Trypanosoma cruzi: Biological Function and Evaluation as Drug Targets

Cited by 5 publications

References 99 publications

Targeting L-Proline Uptake as New Strategy for Anti-chagas Drug Development

Targeting L-Proline Uptake as New Strategy for Anti-chagas Drug Development

Profiling of amines in biological samples using polythioester-functionalized magnetic nanoprobe

Chagas Disease Treatment: From New Therapeutic Targets to Drug Discovery and Repositioning

Contact Info

Product

Resources

About