Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/187534
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Capilla, A. Sergi | - |
dc.contributor.author | Soucek, Richard | - |
dc.contributor.author | Grau, Laura | - |
dc.contributor.author | Romero, Manel | - |
dc.contributor.author | Rubio Martínez, Jaime | - |
dc.contributor.author | Caignard, Daniel H. | - |
dc.contributor.author | Pujol Dilmé, M. Dolors | - |
dc.date.accessioned | 2022-07-11T16:36:01Z | - |
dc.date.available | 2022-07-11T16:36:01Z | - |
dc.date.issued | 2018-02-01 | - |
dc.identifier.issn | 0223-5234 | - |
dc.identifier.uri | http://hdl.handle.net/2445/187534 | - |
dc.description.abstract | A novel group of aryl methyl sulfones based on nonsteroidal anti-inflammatory compounds exhibiting a methyl sulfone instead of the acetic or propionic acid group was designed, synthesized and evaluated in vitro for inhibition against the human cyclooxygenase of COX-1 and COX-2 isoenzymes and in vivo for anti-inflammatory activity using the carrageenan induced rat paw edema model in rats. Also, in vitro chemosensitivity and in vivo analgesic and intestinal side effects were determined for defining the therapeutic and safety profile. Molecular modeling assisted the design of compounds and the interpretation of the experimental results. Biological assay results showed that methyl sulfone compounds 2 and 7 were the most potent COX inhibitors (IC50 between 0.04 and 0.71 M). Also, these highly active methyl sulfones displayed greater COX-2 activity than the parent carboxylic NSAIDs, thus indicating that the replacement of the acetic or propionic acids by a methyl sulfone group enables some of these structures to possess higher COX-2 inhibitory activity than that of the corresponding alkyl carboxylic analogues. The improved inhibitory activity is attributed to the higher flexibility of the sulfone-receptor interaction that enables more profound exploration of the binding site compared with that of acidic analogues. This observation is underpinned by molecular modeling studies that indicates a change in the binding mode or mechanism compared to the standard binding mode displayed by ibuprofen. The most promising compounds 2 and 7 possess a therapeutical profile that enables their chemical scaffolds to be utilized for development of new NSAIDs. | - |
dc.format.extent | 13 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Elsevier Masson SAS | - |
dc.relation.isformatof | Versió postprint del document publicat a: https://doi.org/10.1016/j.ejmech.2017.12.098 | - |
dc.relation.ispartof | European Journal of Medicinal Chemistry, 2018, vol. 145, p. 51-63 | - |
dc.relation.uri | https://doi.org/10.1016/j.ejmech.2017.12.098 | - |
dc.rights | (c) Elsevier Masson SAS, 2018 | - |
dc.source | Articles publicats en revistes (Ciència dels Materials i Química Física) | - |
dc.subject.classification | Medicaments antineoplàstics | - |
dc.subject.classification | Estructura molecular | - |
dc.subject.classification | Isoquinolina | - |
dc.subject.classification | Disseny de medicaments | - |
dc.subject.other | Antineoplastic agents | - |
dc.subject.other | Molecular structure | - |
dc.subject.other | Isoquinoline | - |
dc.subject.other | Drug design | - |
dc.title | Substituted tetrahydroisoquinolines: synthesis, characterization, antitumor activity and other biological properties | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/acceptedVersion | - |
dc.identifier.idgrec | 675964 | - |
dc.date.updated | 2022-07-11T16:36:02Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
Appears in Collections: | Articles publicats en revistes (Ciència dels Materials i Química Física) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
675964.pdf | 1.31 MB | Adobe PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.