Browsing by Author "Valente, Claudia"
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- Dipeptide vinyl sultamsPublication . Valente, Claudia; Guedes, Rita C.; Moreira, Rui; Iley, Jim; Gut, Jiri; Rosenthal, Philip J.The synthesis of phosphonate derivatives of N-phenyl- and N-benzyl-gamma and delta-sultams, and their application in the Wittig-Horner reaction with N-BOC-L-phenylalanine aldehyde to afford E- and Z-isomers, are described. These compounds were further processed to provide five dipeptide vinyl sultams, which were found to be inactive against papain at concentrations up to 50 mu M. In contrast, vinyl sultams demonstrated weak activity against recombinant falcipain-2 and Plasmodium falciparum W2. (c) 2006 Elsevier Ltd. All rights reserved.
- The 1,4-naphthoquinone scaffold in the design of cysteine protease inhibitorsPublication . Valente, Claudia; Moreira, Rul; Guedes, Rita C.; Iley, Jim; Jaffar, Mohammed; Douglas, Kenneth T.A series of 1,4-naphthoquinone derivatives diversely substituted at C-2, C-3, C-5 and C-8, prepared by reaction of amines, amino acids and alcohols with commercial 1,4-naphthoquinones, has been evaluated against papain and bovine spleen cathepsin B. These 1,4-naphthoquinone derivatives were found to be irreversible inhibitors for both cysteine proteases, with second-order rate constants, k(2), ranging from 0.67 to 35.4 M-1 s(-1) for papain, and from 0.54 to 8.03 M-1 s(-1) for cathepsin B. Some derivatives display a hyperbolic dependence of the first-order inactivation rate constant, k(obs) with the inhibitor concentration, indicative of a specific interaction process between enzyme and inhibitor. The chemical reactivity of the compounds towards cysteine as a model thiol is dependent on the naphthoquinone LUMO energy, whereas papain inactivation is not. The 1,4-naphthoquinone derivatives are inactive against the serine protease, porcine pancreatic elastase. (c) 2007 Elsevier Ltd. All rights reserved.