Publication
The 1,4-naphthoquinone scaffold in the design of cysteine protease inhibitors
| dc.contributor.author | Valente, Claudia | |
| dc.contributor.author | Moreira, Rul | |
| dc.contributor.author | Guedes, Rita C. | |
| dc.contributor.author | Iley, Jim | |
| dc.contributor.author | Jaffar, Mohammed | |
| dc.contributor.author | Douglas, Kenneth T. | |
| dc.date.accessioned | 2015-12-30T10:18:16Z | |
| dc.date.available | 2015-12-30T10:18:16Z | |
| dc.date.issued | 2007 | |
| dc.description.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 35.4 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. | |
| dc.format | application/pdf | |
| dc.identifier.citation | BIOORGANIC & MEDICINAL CHEMISTRY. - Vol. 15, n. 15 (AUG 1 2007), p. 5340-5350 | |
| dc.identifier.doi | http://dx.doi.org/10.1016/j.bmc.2007.04.068 | |
| dc.identifier.issn | 0968-0896 | |
| dc.identifier.uri | http://hdl.handle.net/10451/21502 | |
| dc.language.iso | eng | |
| dc.publisher | PERGAMON-ELSEVIER SCIENCE LTD | |
| dc.subject | Biochemistry & Molecular Biology | |
| dc.subject | Chemistry, Medicinal | |
| dc.subject | Chemistry, Organic | |
| dc.title | The 1,4-naphthoquinone scaffold in the design of cysteine protease inhibitors | |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.endPage | 5350 | por |
| oaire.citation.startPage | 5340 | por |
| oaire.citation.title | BIOORGANIC & MEDICINAL CHEMISTRY | por |
| oaire.citation.volume | Vol. 15 | por |
| rcaap.rights | restrictedAccess | |
| rcaap.type | article |