N-alpha-Aminoacyl Colchicines as Promising Anticancer Agents
Ver/ Abrir
Impacto
Scholar |
Otros documentos de la autoría: Marzo Mas, Ana; Conesa Milián, Laura; Noppen, Sam; Liekens, Sandra; Falomir, Eva; Murga, Juan; Carda, Miguel; Marco, J. Alberto
Metadatos
Mostrar el registro completo del ítemcomunitat-uji-handle:10234/9
comunitat-uji-handle2:10234/7053
comunitat-uji-handle3:10234/8639
comunitat-uji-handle4:
INVESTIGACIONMetadatos
Título
N-alpha-Aminoacyl Colchicines as Promising Anticancer AgentsAutoría
Fecha de publicación
2020-12-29Editor
Bentham Science PublishersISSN
1573-4064; 1875-6638Cita bibliográfica
Ana Marzo-Mas, Laura Conesa-Milián, Sam Noppen, Sandra Liekens, Eva Falomir*, Juan Murga, Miguel Carda and Juan A. Marco, “N-alpha-Aminoacyl Colchicines as Promising Anticancer Agents”, Medicinal Chemistry (2021) 17: 21. https://doi.org/10.2174/1573406415666191203112406Tipo de documento
info:eu-repo/semantics/articleVersión de la editorial
https://www.eurekaselect.com/177127/articleVersión
info:eu-repo/semantics/acceptedVersionPalabras clave / Materias
Resumen
Background: In the last years, many efforts have been made to find colchicine derivatives with reduced toxicity. Additionally, the deregulation of amino acid uptake by cancer cells provides an opportunity to improve ... [+]
Background: In the last years, many efforts have been made to find colchicine derivatives with reduced toxicity. Additionally, the deregulation of amino acid uptake by cancer cells provides an opportunity to improve anticancer drug effectiveness.
Objective: To design new colchicine derivatives with reduced cytotoxicity and enhanced selectivity by means of introducing aminoacyl groups.
Methods: 34 colchicine analogues bearing L- and D-amino acid pendants were synthetized and characterized by NMR, IR and MS techniques. Cytotoxicity and antimitotic properties were assessed by spectrophotometry and cell cycle assays. Oncogene downregulation was studied by RTqPCR whereas in vivo studies were performed in SCID mice.
Results: Compounds exhibit high antiproliferative activities at the nanomolar level while being, in general, less cytotoxic than colchicine. Most compounds inhibit the polymerization of tubulin in a way similar to colchicine itself, with L-amino acid derivatives being the most active in the inhibition of tubulin polymerization. All selected compounds caused cell cycle arrest at the G2/M phase when tested at 1 μM. More specifically, Boc-L-proline derivative 6 arrested half of the population and showed one of the highest Selectivity Indexes. Derivatives 1 (Boc-glycine), 27 (D-leucine) and 31 (Boc-glycine-glycine) proved fairly active in downregulating the expression of the c-Myc, hTERT and VEGF oncogenes, with compound 6 (Boc-L-proline) having the highest activity. This compound was shown to exert a potent anti-tumor effect when administered intraperitoneally (LD50 > 100 mg/kg for 6, compared with 2.5 mg/kg for colchicine).
Conclusion: Compound 6 offers an opportunity to be used in cancer therapy with less toxicity problems than colchicine. [-]
Publicado en
Medicinal Chemistry (2021) 17: 21.Entidad financiadora
Ministerio de Economía y Competitividad | Universitat Jaume I | Conselleria d’Educació, Investigació, Cultura i Sport de la Generalitat Valenciana
Código del proyecto o subvención
CTQ2014-52949-P | PI-1B2015-75 | PROMETEO 2013/027
Derechos de acceso
http://rightsstatements.org/vocab/CNE/1.0/
info:eu-repo/semantics/openAccess
info:eu-repo/semantics/openAccess
Aparece en las colecciones
- QUIO_Articles [692]