dc.contributor.author | RADOMSKI, MAREK | en |
dc.contributor.author | WANG, JUN | en |
dc.contributor.author | MEDINA MARTIN, CARLOS | en |
dc.contributor.author | GILMER, JOHN | en |
dc.date.accessioned | 2011-10-05T12:57:50Z | |
dc.date.available | 2011-10-05T12:57:50Z | |
dc.date.issued | 2011 | en |
dc.date.submitted | 2011 | en |
dc.identifier.citation | Jun Wang, Carlos Medina, Marek W. Radomski, John F. Gilmer, N-subsituted homopiperazine barbiturates as gelatinase inhibitors, Bioorganic & Medicinal Chemistry, 19, 16, 2011, 4985-4999 | en |
dc.identifier.other | Y | en |
dc.identifier.uri | http://hdl.handle.net/2262/59834 | |
dc.description | PUBLISHED | en |
dc.description.abstract | Matrix metalloproteinases are implicated in a wide range of pathophysiological processes and potent selective inhibitors for these enzymes continue to be eagerly sought. 5,5-Disubstituted barbiturates hold promise as inhibitor types being stable in vivo and relatively selective for the gelatinases (MMP-2 and MMP-9). In this paper we describe the synthesis of 5-piperazine and -homopiperazine substituted barbiturates. The activity of these compounds as gelatinase inhibitors was evaluated using supernatants from 12-O-tetradecanoylphorbol-13-acetate (PMA) - stimulated HT-1080 cells as well as using recombinant human MMPs. N-acyl homopiperazine compounds were found to be potent inhibitors of the gelatinases (range in nM) and generally more potent than the corresponding piperazine analogs. The panel of N-acyl homopiperazines was enlarged in order to exploit differences between the gelatinases at the S2? site in order to design MMP-2- or MMP-9-selective inhibitors. Compounds in this group exhibited single digit nano-molar potency and some selectivity between the two enzymes. Representative potent compounds were effective inhibitors of cancer cell migration. | en |
dc.format.extent | 4985-4999 | en |
dc.language.iso | en | en |
dc.relation.ispartofseries | Bioorganic & Medicinal Chemistry | en |
dc.relation.ispartofseries | 19 | en |
dc.relation.ispartofseries | 16 | en |
dc.rights | Y | en |
dc.subject | Biochemistry | en |
dc.subject | Matrix metalloproteinases | en |
dc.title | N-subsituted homopiperazine barbiturates as gelatinase inhibitors | en |
dc.type | Journal Article | en |
dc.contributor.sponsor | Science Foundation Ireland (SFI) | en |
dc.type.supercollection | scholarly_publications | en |
dc.type.supercollection | refereed_publications | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/radomskm | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/martinc2 | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/gilmerjf | en |
dc.identifier.rssinternalid | 73774 | en |
dc.identifier.rssuri | http://dx.doi.org/10.1016/j.bmc.2011.06.055 | en |