Results 141 to 150 of about 1,668 (161)

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
openaire   +2 more sources

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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Uncovering false positives on a virtual screening search for cruzain inhibitors

Bioorganic & Medicinal Chemistry Letters, 2008
Some unexpected promiscuous inhibitors were observed in a virtual screening protocol applied to select cruzain inhibitors from the ZINC database. Physical-chemical and pharmacophore model filters were used to reduce the database size. The selected compounds were docked into the cruzain active site. Six hit compounds were tested as inhibitors.
Alberto, Malvezzi, Leandro, de Rezende, Mario Augusto, Izidoro, Maria Helena Sedenho, Cezari, Luiz, Juliano, Antonia, do Amaral   +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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Potent second generation vinyl sulfonamide inhibitors of the trypanosomal cysteine protease cruzain

Bioorganic & Medicinal Chemistry Letters, 2001
A new family of potent N-alkoxyvinylsulfonamide inhibitors of cruzain have been developed. Inhibitor 13 has a second order inactivation rate constant of 6,480,000s(-1)M(-1) versus cruzain, and is also highly effective against Trypanosoma cruzi trypomastigotes in a tissue culture assay.
W R, Roush, J, Cheng, B, Knapp-Reed, A, Alvarez-Hernandez, J H, McKerrow, E, Hansell, J C, Engel   +6 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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Discovery of Novel Inhibitors of Cruzain Cysteine Protease of Trypanosoma cruzi

Current Medicinal Chemistry
Abstract: Chagas disease (CD) is a parasitic disease endemic in several developing coun-tries. According to the World Health Organization, approximately 6-8 million people worldwide are inflicted by CD. The scarcity of new drugs, mainly for the chronic phase, is the main reason for treatment limitation in CD.
João Lucas Bruno Prates, Juliana Romano Lopes, Chung Man Chin, Elizabeth Igne Ferreira, Jean Leandro dos Santos, Cauê Benito Scarim   +5 more
openaire   +2 more sources

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
openaire   +3 more sources

Cruzain inhibitors: efforts made, current leads and a structural outlook of new hits

Drug Discovery Today, 2015
Human African trypanosomiasis and Chagas disease are the main causes of heart failure in developing countries. The disadvantages of current therapy include: undesirable side-effects, resistance, lack of efficacy on late-stage disease and lack of pediatric formulations.
Karina, Martinez-Mayorga, Kendall G, Byler, Ariadna I, Ramirez-Hernandez, Diana E, Terrazas-Alvares   +3 more
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Cruzain inhibition by terpenoids

Planta Medica, 2008
BR Agius, SL Stokes, LR Richter, WN Setzer   +3 more
openaire   +1 more source