1256776-45-0Relevant articles and documents
Endoperoxide carbonyl falcipain 2/3 inhibitor hybrids: Toward combination chemotherapy of malaria through a single chemical entity
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.
supporting information; experimental part, p. 8202 - 8206 (2011/02/26)
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 carbonyl-masking 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.
