Results 151 to 160 of about 1,018 (177)

The Crystal Structure of Cruzain: A Therapeutic Target for Chagas' Disease

Journal of Molecular Biology, 1995
Trypanosoma cruzi, a protozoan parasite, is the etiologic agent of American trypanosomiasis or Chagas' disease. Chagas' disease afflicts more than 24 million individuals in South and Central America producing a debilitating life-long disease. It is the leading cause of heart failure in many Latin American countries.
M E, McGrath, A E, Eakin, J C, Engel, J H, McKerrow, C S, Craik, R J, Fletterick   +5 more
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Molecular Docking Studies Applied to a Dataset of Cruzain Inhibitors

Current Computer-Aided Drug Design, 2018
Chagas' disease is one of the main causes of heart failure in developing countries. The disadvantages of current therapy include the undesirable side-effects, resistance, and therapeutic adhesion. The development of new efficient and safe drugs is, therefore, an issue of extreme importance.In order to gain a better understanding of how the compounds ...
Edeildo Ferreira, da Silva-Junior, Paulo Henrique, Barcellos Franca, Frederico Favaro, Ribeiro, Francisco Jaime, Bezerra Mendonca-Junior, Luciana, Scotti, Marcus Tullius, Scotti, Thiago Mendonca, de Aquino, Joao Xavier, de Araujo-Junior   +7 more
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Structure-Based Optimization of Quinazolines as Cruzain and TbrCATL Inhibitors

Journal of Medicinal Chemistry, 2021
The cysteine proteases, cruzain and TbrCATL (rhodesain), are therapeutic targets for Chagas disease and Human African Trypanosomiasis, respectively. Among the known inhibitors for these proteases, we have described N4-benzyl-N2-phenylquinazoline-2,4-diamine (compound 7 in the original publication, 1a in this study), as a competitive cruzain inhibitor ...
Elany Barbosa da Silva, Débora A. Rocha, Isadora S. Fortes, Wenqian Yang, Ludovica Monti, Jair L. Siqueira-Neto, Conor R. Caffrey, James McKerrow, Saulo F. Andrade, Rafaela S. Ferreira   +9 more
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Assessment of the Cruzain Cysteine Protease Reversible and Irreversible Covalent Inhibition Mechanism

Journal of Chemical Information and Modeling, 2020
Reversible and irreversible covalent ligands are advanced cysteine protease inhibitors in the drug development pipeline. K777 is an irreversible inhibitor of cruzain, a necessary enzyme for the survival of the Trypanosoma cruzi (T. cruzi) parasite, the causative agent of Chagas disease.
José Rogério A. Silva, Lorenzo Cianni, Deborah Araujo, Pedro Henrique Jatai Batista, Daniela de Vita, Fabiana Rosini, Andrei Leitão, Jerônimo Lameira, Carlos Alberto Montanari   +8 more
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Cruzain Inhibitors: State-of-Art of Novel Synthetic Strategies

Current Organic Chemistry, 2023
Abstract: Concerned about a million people are infected worldwide, and other millions are living at risk zones of infection. Chagas disease causes 10 000 deaths annually, and the discovery of safe and effective drugs on a nanomolar scale has been headlined as a crucial goal by the worldwide research community and international health agencies ...
Pedro Alves Bezerra Morais, Gustavo Henrique Goulart Trossini   +1 more
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Impact of different protonation states on virtual screening performance against cruzain

Chemical Biology & Drug Design, 2022
AbstractThe cysteine protease cruzain is a Chagas disease target, exploited in computational studies. However, there is no consensus on the protonation states of the active site residues Cys25, His162, and Glu208 at the enzyme's active pH range. We evaluated the impact of different protonation states of these residues on docking calculations. Through a
Viviane Corrêa, Santos, Augusto César Broilo, Campos, Birgit J, Waldner, Klaus R, Liedl, Rafaela Salgado, Ferreira   +4 more
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Computational study on the inhibition mechanism of cruzain by nitrile-containing molecules

Journal of Molecular Graphics and Modelling, 2012
Cysteine proteases from parasites as well as from mammals are promising drug targets for parasitic infections and systemic human diseases, respectively. Many reversible and irreversible inhibitors of this very large class of proteins have been designed.
Oscar, Méndez-Lucio, Antonio, Romo-Mancillas, José L, Medina-Franco, Rafael, Castillo   +3 more
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CRUZAIN The Path from Target Validation to the Clinic

Advances in experimental medicine and biology, 2011
Cruzain is the major papain-like cysteine protease of Trypanosoma cruzi, the etiological agent causing Chagas' disease in humans in South America. Cruzain is indispensable for the survival and propagation of this protozoan parasite and therefore, it has attracted considerable interest as a potential drug target.
Sajid, M., Robertson, S.A., Brinen, L.S., McKerrow, J.H., Robinson, M.W., Dalton, J.P.   +5 more
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Crystal structures of reversible ketone-Based inhibitors of the cysteine protease cruzain

Bioorganic & Medicinal Chemistry, 2003
The crystal structures of two hydroxymethyl ketone inhibitors complexed to the cysteine protease cruzain have been determined at 1.1 and 1.2 A resolution, respectively. These high resolution crystal structures provide the first structures of non-covalent inhibitors bound to cruzain.
Lily, Huang, Linda S, Brinen, Jonathan A, Ellman   +2 more
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Evaluation of quinoxaline compounds as ligands of a site adjacent to S2 (AS2) of cruzain

Bioorganic & Medicinal Chemistry Letters, 2019
The binding of ten quinoxaline compounds (1-10) to a site adjacent to S2 (AS2) of cruzain (CRZ) was evaluated by a protocol that include a first analysis through docking experiments followed by a second analysis using the Molecular Mechanics-Poisson-Boltzmann Surface Area method (MM-PBSA). Through them we demonstrated that quinoxaline compounds bearing
Lucas Fabian, M. Florencia Martini, Emir Salas Sarduy, Darío A. Estrin, Albertina G. Moglioni   +4 more
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