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The 1,4-naphthoquinone scaffold in the design of cysteine protease inhibitors
- Source :
-
Bioorganic & Medicinal Chemistry . Aug2007, Vol. 15 Issue 15, p5340-5350. 11p. - Publication Year :
- 2007
-
Abstract
- Abstract: 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 35.4M−1 s−1 for papain, and from 0.54 to 8.03M−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. [Copyright &y& Elsevier]
- Subjects :
- *PHYSICAL sciences
*BIOORGANIC chemistry
*SCIENCE
*PHARMACEUTICAL chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 09680896
- Volume :
- 15
- Issue :
- 15
- Database :
- Academic Search Index
- Journal :
- Bioorganic & Medicinal Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 25319525
- Full Text :
- https://doi.org/10.1016/j.bmc.2007.04.068