Total synthesis and antiproliferative activity screening of (±)-aplicyanins A, B and E and related analogs

The first total synthesis of the indole alkaloids ()-aplicyanins A, B and E, plus seventeen analogs, all in racemic form is reported. Modifications to the parent compound included changing the number of bromine substituents on the indole, the groups on the indole nitrogen (H, Me or OMe), and/or the...

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Detalles Bibliográficos
Autores: Sísa, Miroslav, Pla Queral, Daniel, Altuna, Marta, Francesch, Andrés, Cuevas, Carmen, Albericio Palomera, Fernando, Álvarez Domingo, Mercedes
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2009
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/56023
Acceso en línea:https://hdl.handle.net/2445/56023
Access Level:acceso abierto
Palabra clave:Medicaments antineoplàstics
Síntesi de fàrmacs
Alcaloides
Metabòlits marins
Antineoplastic agents
Drug synthesis
Alkaloids
Marine metabolites
Descripción
Sumario:The first total synthesis of the indole alkaloids ()-aplicyanins A, B and E, plus seventeen analogs, all in racemic form is reported. Modifications to the parent compound included changing the number of bromine substituents on the indole, the groups on the indole nitrogen (H, Me or OMe), and/or the oxidation level of the heterocyclic core tetrahydropyrimidine. Each compound was screened against three human tumor cell lines, and fourteen of the newly synthesized compounds showed considerable cytotoxicity. The assay results were used to establish structure-activity relationships. These results suggest that the acetyl group moiety on the imine nitrogen, and the bromine at position 5 of the indole, are both critical to activity.