Valente, ClaudiaMoreira, RulGuedes, Rita C.Iley, JimJaffar, MohammedDouglas, Kenneth T.2015-12-302015-12-302007BIOORGANIC & MEDICINAL CHEMISTRY. - Vol. 15, n. 15 (AUG 1 2007), p. 5340-53500968-0896http://hdl.handle.net/10451/21502A 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.application/pdfengBiochemistry & Molecular BiologyChemistry, MedicinalChemistry, Organicjournal articlehttp://dx.doi.org/10.1016/j.bmc.2007.04.068