dc.contributor.author | Espejo-Román, Jose M. | |
dc.contributor.author | Rubio Ruiz, Belén | |
dc.contributor.author | Chayah-Ghaddab, Meriem | |
dc.contributor.author | Vega-Gutierrez, Carlos | |
dc.contributor.author | García García, Gracia | |
dc.contributor.author | Muguruza-Montero, Arantza | |
dc.contributor.author | Domene, Carmen | |
dc.contributor.author | Sánchez-Martín, Rosario M. | |
dc.contributor.author | Cruz-López, Olga | |
dc.contributor.author | Conejo-García, Ana | |
dc.date.accessioned | 2024-02-22T17:10:16Z | |
dc.date.available | 2024-02-22T17:10:16Z | |
dc.date.issued | 2023 | |
dc.identifier.issn | 0223-5234 | spa |
dc.identifier.uri | https://hdl.handle.net/10641/4082 | |
dc.description.abstract | Hyaluronic acid (HA) plays a crucial role in tumor growth and invasion through its interaction with cluster of differentiation 44 (CD44), a non-kinase transmembrane glycoprotein, among other hyaladherins. CD44 expression is elevated in many solid tumors, and its interaction with HA is associated with cancer and angiogenesis. Despite efforts to inhibit HA-CD44 interaction, there has been limited progress in the development of small molecule inhibitors. As a contribution to this endeavour, we designed and synthesized a series of N-aryltetrahydroisoquinoline derivatives based on existing crystallographic data available for CD44 and HA. Hit 2e was identified within these structures for its antiproliferative effect against two CD44+ cancer cell lines, and two new analogs (5 and 6) were then synthesized and evaluated as CD44-HA inhibitors by applying computational and cell-based CD44 binding studies. Compound 2-(3,4,5-trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinolin-5-ol (5) has an EC50 value of 0.59 μM against MDA-MB-231 cells and is effective to disrupt the integrity of cancer spheroids and reduce the viability of MDA-MB-231 cells in a dose-dependent manner. These results suggest lead 5 as a promising candidate for further investigation in cancer treatment. | spa |
dc.language.iso | eng | spa |
dc.publisher | European Journal of Medicinal Chemistry | spa |
dc.rights | Atribución-NoComercial-SinDerivadas 3.0 España | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.subject | Hyaluronic acid | spa |
dc.subject | Cluster of differentiation 44 | spa |
dc.subject | Tetrahydroisoquinoline | spa |
dc.subject | Molecular dynamics simulations | spa |
dc.subject | Antiproliferative effect | spa |
dc.subject | Three-dimensional cancer model evaluation | spa |
dc.title | N-aryltetrahydroisoquinoline derivatives as HA-CD44 interaction inhibitors: Design, synthesis, computational studies, and antitumor effect. | spa |
dc.type | journal article | spa |
dc.type.hasVersion | AM | spa |
dc.rights.accessRights | open access | spa |
dc.description.extent | 5033 KB | spa |
dc.identifier.doi | 10.1016/j.ejmech.2023.115570 | spa |
dc.relation.publisherversion | https://www.sciencedirect.com/science/article/pii/S0223523423005366 | spa |