dc.creator | Romero Hernández, Laura L. | es |
dc.creator | Merino Montiel, Penélope | es |
dc.creator | Meza Reyes, Socorro | es |
dc.creator | Vega Baez, José Luis | es |
dc.creator | López López, Óscar | es |
dc.creator | Padrón, José M. | es |
dc.creator | Montiel Smith, Sara | es |
dc.date.accessioned | 2024-02-06T16:33:44Z | |
dc.date.available | 2024-02-06T16:33:44Z | |
dc.date.issued | 2018-01-01 | |
dc.identifier.citation | Romero Hernández, L.L., Merino Montiel, P., Meza Reyes, S., Vega Baez, J.L., López López, Ó., Padrón, J.M. y Montiel Smith, S. (2018). Synthesis of unprecedented steroidal spiro heterocycles as potential antiproliferative drugs. European Journal of Medicinal Chemistry, 143, 21-32. https://doi.org/10.1016/j.ejmech.2017.10.063. | |
dc.identifier.issn | 0223-5234 | es |
dc.identifier.issn | 1768-3254 | es |
dc.identifier.uri | https://hdl.handle.net/11441/154735 | |
dc.description.abstract | Herein we report the straightforward preparation of novel conformationally-restricted steroids from trans-androsterone and estrone, decorated with spiranic oxazolidin-2-one or 2-aminooxazoline motifs at C-17 as potential antiproliferative agents. Such unprecedented pharmacophores were accessed using an aminomethylalcohol derivative at C-17 as the key intermediate; reaction of such functionality with triphosgene, or conversion into N-substituted thioureas, followed by an intramolecular cyclodesulfurization reaction promoted by yellow HgO, furnished such spirocycles in excellent yields. Title compounds were tested in vitro against a panel of six human tumor cell lines, named A549 (non-small cell lung), HBL-100 (breast), HeLa (cervix), SW1573 (non-small cell lung), T-47D (breast) and WiDr (colon), and the results were compared with steroidal chemotherapeutic agents (abiraterone and galeterone); the A-ring of the steroidal backbone, the nature of the heterocycle and the N-substituents proved to be essential motifs for establishing structure-activity relationships concerning not only the potency but also the selectivity against tumor cell lines. Estrone derivatives, particularly those bearing a spiranic 2-aminooxazoline scaffold were found to be the most active compounds, with GI50 values ranging from the low micromolar to the submicromolar level (0.34–1.5 μM). Noteworthy, the lead compounds showed a remarkable increase in activity against the resistant cancer cell lines (T-47D and WiDr) compared to the anticancer reference drugs (up to 120-fold). | es |
dc.description.sponsorship | CONACYT-México 240329 | es |
dc.format | application/pdf | es |
dc.format.extent | 35 p. | es |
dc.language.iso | eng | es |
dc.publisher | Elsevier | es |
dc.relation.ispartof | European Journal of Medicinal Chemistry, 143, 21-32. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Antiproliferative activity | es |
dc.subject | Heterocycles | es |
dc.subject | Oxazolidine | es |
dc.subject | Oxazoline | es |
dc.subject | Steroids | es |
dc.title | Synthesis of unprecedented steroidal spiro heterocycles as potential antiproliferative drugs | es |
dc.type | info:eu-repo/semantics/article | es |
dc.type.version | info:eu-repo/semantics/acceptedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Química orgánica | es |
dc.relation.projectID | 240329 | es |
dc.relation.publisherversion | https://doi.org/10.1016/j.ejmech.2017.10.063 | es |
dc.identifier.doi | 10.1016/j.ejmech.2017.10.063 | es |
dc.journaltitle | European Journal of Medicinal Chemistry | es |
dc.publication.volumen | 143 | es |
dc.publication.initialPage | 21 | es |
dc.publication.endPage | 32 | es |
dc.contributor.funder | CONACYT-México | es |