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Discovery of indolizine lactones as anticancer agents and their optimization through late-stage functionalization

Indolizines fused with a seven-member lactone ring were identified as a promising scaffold in the search for new anticancer agents. Through a modular synthetic sequence, a library of cis and trans indolizines lactones had their antiproliferative activity evaluated against hormone-refractory prostate...

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Detalles Bibliográficos
Autores principales: da Silva, Thiago Sabino, da Silva Souza, Matheus, Andricopulo, Adriano Defini, Coelho, Fernando
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10321224/
https://www.ncbi.nlm.nih.gov/pubmed/37416908
http://dx.doi.org/10.1039/d3ra03395c
Descripción
Sumario:Indolizines fused with a seven-member lactone ring were identified as a promising scaffold in the search for new anticancer agents. Through a modular synthetic sequence, a library of cis and trans indolizines lactones had their antiproliferative activity evaluated against hormone-refractory prostate DU-145 and triple-negative breast MDA-MB-231 cancer cell lines. A methoxylated analogue was identified as an initial hit against MDA-MB-231 and late-stage functionalization of the indolizine core led to analogues within potencies up to twenty times higher than the parent precursor.