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Trypanothione Reductase and Superoxide Dismutase as Current Drug Targets for Trypanosoma cruzi: An Overview of Compounds with Activity against Chagas Disease.
Curr Med Chem. 2017 May 31; 24(11):1066-1138.CM

Abstract

It has been over a century since Carlos Chagas discovered the Trypanosoma cruzi (T. cruzi) as the causative agent of Chagas disease (CD), a neglected tropical disease with several socioeconomic, epidemiological and human health repercussions. Currently, there are only two commercialized drugs to treat CD in acute phase, nifurtimox and benznidazol, with several adverse side effects. Thus, new orally available and safe drugs for this parasitic infection are urgently required. One strategy of great importance in new drug discovery programmes is based on the search of molecules enabling to interfere with enzymes involved in T. cruzi metabolism. This review will focus on two of the most promising targets for the therapy of CD: trypanothione reductase (TR) and the iron-containing superoxide dismutase (Fe- SOD), which protect the parasite against oxidative damage by reactive oxygen species. A brief comparison of the function, mechanism of action and the active sites between T. cruzi TR and Fe-SOD with their analogues enzymes in human, glutathione reductase (GR) and the corresponding SODs, will be discussed. This review will also summarize the recent development and structure-activity relationships of novel compounds reported for their ability to selectively inhibit these targets, aiming to define molecular bases in the search for new effective treatment of CD.

Authors+Show Affiliations

Universidad de Navarra, Instituto de Salud Tropical (ISTUN), Campus Universitario, 31008, Pamplona. Spain.Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia y Nutrición, Universidad de Navarra, Campus Universitario, 31008, Pamplona. Spain.Universidad de Navarra, Facultad de Farmacia y Nutrición, Departamento de Química Orgánica y Farmacéutica, Campus Universitario, 31008, Pamplona. Spain.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

28025938

Citation

Beltran-Hortelano, Ivan, et al. "Trypanothione Reductase and Superoxide Dismutase as Current Drug Targets for Trypanosoma Cruzi: an Overview of Compounds With Activity Against Chagas Disease." Current Medicinal Chemistry, vol. 24, no. 11, 2017, pp. 1066-1138.
Beltran-Hortelano I, Perez-Silanes S, Galiano S. Trypanothione Reductase and Superoxide Dismutase as Current Drug Targets for Trypanosoma cruzi: An Overview of Compounds with Activity against Chagas Disease. Curr Med Chem. 2017;24(11):1066-1138.
Beltran-Hortelano, I., Perez-Silanes, S., & Galiano, S. (2017). Trypanothione Reductase and Superoxide Dismutase as Current Drug Targets for Trypanosoma cruzi: An Overview of Compounds with Activity against Chagas Disease. Current Medicinal Chemistry, 24(11), 1066-1138. https://doi.org/10.2174/0929867323666161227094049
Beltran-Hortelano I, Perez-Silanes S, Galiano S. Trypanothione Reductase and Superoxide Dismutase as Current Drug Targets for Trypanosoma Cruzi: an Overview of Compounds With Activity Against Chagas Disease. Curr Med Chem. 2017 May 31;24(11):1066-1138. PubMed PMID: 28025938.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Trypanothione Reductase and Superoxide Dismutase as Current Drug Targets for Trypanosoma cruzi: An Overview of Compounds with Activity against Chagas Disease. AU - Beltran-Hortelano,Ivan, AU - Perez-Silanes,Silvia, AU - Galiano,Silvia, PY - 2016/09/09/received PY - 2016/12/02/revised PY - 2016/12/23/accepted PY - 2016/12/28/pubmed PY - 2017/9/9/medline PY - 2016/12/28/entrez KW - Chagas disease KW - Trypanosoma cruzi KW - drug development KW - drug targets KW - structure-activity relationship KW - superoxide dismutase KW - trypanocidal activity KW - trypanothione reductase SP - 1066 EP - 1138 JF - Current medicinal chemistry JO - Curr. Med. Chem. VL - 24 IS - 11 N2 - It has been over a century since Carlos Chagas discovered the Trypanosoma cruzi (T. cruzi) as the causative agent of Chagas disease (CD), a neglected tropical disease with several socioeconomic, epidemiological and human health repercussions. Currently, there are only two commercialized drugs to treat CD in acute phase, nifurtimox and benznidazol, with several adverse side effects. Thus, new orally available and safe drugs for this parasitic infection are urgently required. One strategy of great importance in new drug discovery programmes is based on the search of molecules enabling to interfere with enzymes involved in T. cruzi metabolism. This review will focus on two of the most promising targets for the therapy of CD: trypanothione reductase (TR) and the iron-containing superoxide dismutase (Fe- SOD), which protect the parasite against oxidative damage by reactive oxygen species. A brief comparison of the function, mechanism of action and the active sites between T. cruzi TR and Fe-SOD with their analogues enzymes in human, glutathione reductase (GR) and the corresponding SODs, will be discussed. This review will also summarize the recent development and structure-activity relationships of novel compounds reported for their ability to selectively inhibit these targets, aiming to define molecular bases in the search for new effective treatment of CD. SN - 1875-533X UR - https://www.unboundmedicine.com/medline/citation/28025938/Trypanothione_Reductase_and_Superoxide_Dismutase_as_Current_Drug_Targets_for_Trypanosoma_cruzi:_An_Overview_of_Compounds_with_Activity_against_Chagas_Disease_ L2 - http://www.eurekaselect.com/148729/article DB - PRIME DP - Unbound Medicine ER -