Publication
Aspartic vinyl sulfones: inhibitors of a caspase-3-dependent pathway
| dc.contributor.author | Glória, Paulo M. C. | |
| dc.contributor.author | Coutinho, Isabel | |
| dc.contributor.author | Gonçalves, Lídia M. | |
| dc.contributor.author | Baptista, Cristina | |
| dc.contributor.author | Soares, Joana | |
| dc.contributor.author | Newton, Ana S. | |
| dc.contributor.author | Moreira, Rui | |
| dc.contributor.author | Saraiva, Lucília | |
| dc.contributor.author | Santos, Maria M. M. | |
| dc.date.accessioned | 2011-08-01T12:52:49Z | |
| dc.date.available | 2011-08-01T12:52:49Z | |
| dc.date.issued | 2011 | |
| dc.date.updated | 2011-06-09T11:47:33Z | |
| dc.description.abstract | In this article we describe an expanded structureeactivity relationship study for vinyl sulfones as caspase-3 inhibitors, a topic virtually unexplored in the existing literature. Most remarkably, and to our surprise, tripeptidyl vinyl sulfones were not active for caspase-3, opposite to other examples described in literature for peptidyl vinyl sulfones as potent cysteine protease inhibitors of clan CA. Moreover, the caspase-3 inhibitory activity of vinyl sulfones using an in vitro assay was then confirmed using a yeast cell-based assay. The results show that Fmoc-protected vinyl sulfones containing only the Asp moiety are inhibitors of a caspase-3-dependent pathway and the IC50 values obtained in the yeast assay are in the same order of magnitude of that obtained with the caspase-3 inhibitor tetrapeptidyl chloromethyl ketone, Ac-DEVD-CMK. This observation is consistent with appropriate cell permeability properties displayed by the vinyl sulfone inhibitors, as reflected by log P values ranging from 1.1 to 3.4. Overall, these results suggest that vinyl sulfones containing Asp at P1 should be considered for further optimization as caspase inhibitors and modulators of caspase-3-dependent pathways. | por |
| dc.identifier.citation | Paulo M. C. Glória; Coutinho, I; Lídia M. Gonçalves; Baptista, C; Soares, J; Ana S. Newton; Moreira, R; Saraiva, L; Santos, Maria Manuel Duque Vieira Marques dos. Aspartic vinyl sulfones: inhibitors of a caspase-3-dependent pathway, European Journal of Medicinal Chemistry, 46, 2141-2146, 2011. | por |
| dc.identifier.issn | 0223-5234 | |
| dc.identifier.uri | http://dx.doi.org/10.1016/j.ejmech.2011.02.067 | |
| dc.identifier.uri | http://hdl.handle.net/10451/3843 | |
| dc.language.iso | eng | por |
| dc.peerreviewed | yes | por |
| dc.publisher | Elsevier | por |
| dc.relation.publisherversion | http://www.sciencedirect.com/science/article/pii/S0223523411001954 | por |
| dc.subject | Vinyl sulfone | por |
| dc.subject | Caspase-3 inhibitor | por |
| dc.subject | Michael acceptor | por |
| dc.subject | Irreversible inhibitor | por |
| dc.subject | Yeast cell-based assay | por |
| dc.title | Aspartic vinyl sulfones: inhibitors of a caspase-3-dependent pathway | por |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.endPage | 2146 | por |
| oaire.citation.startPage | 2141 | por |
| oaire.citation.title | European Journal of Medicinal Chemistry | por |
| rcaap.rights | restrictedAccess | por |
| rcaap.type | article | por |