Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.1/4219
Título: Endoperoxide carbonyl falcipain 2/3 inhibitor hybrids: toward combination chemotherapy of malaria through a single chemical entity
Autor: Gibbons, Peter
Verissimo, Edite
Araújo, Nuna C.
Barton, Victoria
Nixon, Gemma L.
Amewu, Richard K.
Chadwick, J.
Stocks, Paul A.
Biagini, Giancarlo A.
Srivastava, Abhishek
Rosenthal, Philip J.
Gut, Jiri
Guedes, Rita C.
Moreira, Rui
Sharma, Raman
Berry, Neil
Cristiano, Maria Lurdes Santos
Shone, Alison E.
Ward, Stephen A.
O'Neill, Paul M.
Data: 2010
Editora: American Chemical Society
Citação: Gibbons, Peter; Verissimo, Edite; Araujo, Nuna C.; Barton, Victoria; Nixon, Gemma L.; Amewu, Richard K.; Chadwick, James; Stocks, Paul A.; Biagini, Giancarlo A.; Srivastava, Abhishek; Rosenthal, Philip J.; Gut, Jiri; Guedes, Rita C.; Moreira, Rui; Sharma, Raman; Berry, Neil; Cristiano, M. Lurdes S.; Shone, Alison E.; Ward, Stephen A.; O’Neill, Paul M. Endoperoxide Carbonyl Falcipain 2/3 Inhibitor Hybrids: Toward Combination Chemotherapy of Malaria through a Single Chemical Entity, Journal of Medicinal Chemistry, 53, 22, 8202-8206, 2010.
Resumo: We extend our approach of combination chemotherapy through a single prodrug entity (O’Neill et al. Angew. Chem., Int. Ed. 2004, 43, 4193) by using a 1,2,4-trioxolane as a protease inhibitor carbonylmasking group. These molecules are designed to target the malaria parasite through two independent mechanisms of action: iron(II) decomposition releases the carbonyl protease inhibitor and potentially cytotoxic C-radical species in tandem. Using a proposed target “heme”, we also demonstrate heme alkylation/carbonyl inhibitor release and quantitatively measure endoperoxide turnover in parasitized red blood cells.
Peer review: yes
URI: http://hdl.handle.net/10400.1/4219
DOI: http://dx.doi.org/10.1021/jm1009567
ISSN: 0022-2623
Versão do Editor: http://pubs.acs.org/jmc
Aparece nas colecções:CCM2-Artigos (em revistas ou actas indexadas)

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